Made available in DSpace on 2016-08-10T10:38:42Z (GMT). No. of bitstreams: 1 KLEBER SANTIAGO FREITAS E SILVA.pdf: 1080005 bytes, checksum: 9dfcb821b9cd1574718e2442cabc533b (MD5) Previous issue date: 2013-02-18 / In healthy women, a great number of intra and extracellular controls prevent the attachment and proliferation of ectopic endometrial cells. In endometriosis, abnormalities in those controls can lead to the survival of endometrial cells and consequently their attachment to the peritoneal cavity and disease progression. Endometrial cells with genetic polymorphisms respond to local signals, and they proliferate instead of undergoing apoptosis. The products of these abnormal cells stimulate the invasion of tissues and induce an inflammatory response. The disease has a complex trait and it is related to several factors such as genetic, immunological and environmental. This study examined six polymorphisms presented by six different genes (p53; Estrogen Receptor β; Progesterone receptor; GSTM1; GSTT1; CYP1A1). We obtained the polymorphic genotype frequencies from the same 50 patients for all genes and we analyzed them using the Fisher's Exact Test or G Test. First we analyzed the genes in a group of two and subsequently in a group of three. We found significant association between polymorphisms in six pairs of genes (p53-Erβ with frequency 5.9 times higher in the experimental group; p53-GSTM1, 2.39 times higher; p53-CYP1A1 with 65.5% of the patients with the polymorphism; ERβ-PROGINS 3.0 times higher in the experimental group; GSTM1-PROGINS and GSTT1-CYP1A1 both with 31.25% of the patients with the polymorphism). Positive results were found in 15 situations when genes were analyzed in a group of three; the most significant result corresponding to the polymorphisms of the genes p53, Erβ e GSTM1 with 20% of the patients carrying these polymorphisms; PROGINS, Erβ e GSTM1 with 18% and p53, Erβ e PROGINS with 12%. The results support the idea that the presence of polymorphisms in more than one endometriosis-related gene can lead to the onset of the disease and its progression. Studies should aim at these genes in order to understand the relationship among them more clearly and the possibility of developing new diagnostic techniques based on molecular markers of these genes. / Controles intra e extracelulares impedem a implantação e a proliferação de células endometriais ectópicas nas mulheres saudáveis. Anormalidades em quaisquer desses controles levam à sobrevida dessas células, implantação e a consequente progressão da Endometriose. Células endometriais com polimorfismos genéticos respondem a sinais locais e se proliferam não sofrendo apoptose. Os produtos dessas células anormais estimulam a invasão de tecidos e induzem respostas inflamatórias. A doença é complexa e relacionada a fatores como o genético, o imunológico e o ambiental. Este trabalho analisou seis polimorfismos de seis diferentes genes (p53; Receptor β de estrógeno; Receptor de progesterona; GSTM1; GSTT1; CYP1A1). As frequências dos genótipos polimórficos foram obtidas das mesmas 50 pacientes para todos os genes e analisadas pelo Teste Exato de Fisher ou Teste G. Os genes foram analisados dois a dois e posteriormente três a três. Resultados significativos foram encontrados para seis pares de genes (p53- REβ com frequência de polimorfismo 5,9 vezes maior no grupo endometriose; p53-GSTM1 com frequência 2,39 vezes maior; p53-CYP1A1 com 65,5% das pacientes com endometriose apresentando os polimorfismos; REβ-PROGINS com frequência 3,0 vezes maior; GSTM1-PROGINS e GSTT1-CYP1A1, ambos com 31,25% das pacientes do grupo endometriose apresentando os polimorfismos). Em 15 situações quando os genes foram analisados três a três o p foi menor que 0,05. Os polimorfismos de maior frequência foram dos genes p53, REβ e GSTM1 com 20% das pacientes com endometriose apresentando esses polimorfismos; PROGINS, REβ e GSTM1 com 18% e p53, REβ e PROGINS com 12%. Esses resultados corroboram a ideia de que a presença de polimorfismos em mais de um gene relacionado à endometriose pode levar ao aparecimento e deselvolvimento da doença. Estudos devem ser direcionados a esses genes na tentativa de compreender mellhor a relação entre eles e o possível desenvolvimento de novas técnicas de diagnóstico baseada nos marcadores moleculares desses mesmos genes.

La protéine kinase D1, PKD1, est une nouvelle sérine/thréonine kinase activée par de nombreux mitogènes et dérégulée dans de nombreux types de cancers dont le cancer du sein, ce qui suggère un rôle de cette kinase dans la prolifération cellulaire et la tumorigenèse. Cependant, le rôle précis et les cibles de PKD1 ne sont pas encore bien connus. Au cours de ce travail, nous avons tout d’abord démontré que PKD1 est activée par les facteurs de croissance épidermique (EGF) et fibroblastique (FGF) et qu’elle régule la voie de signalisation de l’insulin-like Growth Factor-I (IGF-I). D’autre part, nos résultats démontrent que PKD1 favorise les propriétés pro-prolifératives et pro-tumorales des cellules MCF-7 dérivées d’un adénocarcinome mammaire humain estrogéno-dépendant. Ces mécanismes mettent en jeu des voies de signalisation dépendantes de protéines kinases (la voie MEK/ERK) et hormonales (la voie estrogène/REα). Ainsi, l’ensemble de ce travail fait apparaître PKD1 comme une nouvelle cible thérapeutique anti-tumorale potentielle. / Protein kinase D1, PKD1, is a novel serine/threonine kinase which can be activated by mitogens and whose expression is altered in many tumors such as breast cancer, suggesting a role for this kinase in cancer development. However, its precise role and targets are still unclear. Our study identified PKD1 as a new regulatory kinase implicated in the control of IGF-I signal transduction pathway. Furthermore, we showed that PKD1 enhances estrogen-dependent MCF-7 breast cancer cell proliferation and tumorigenesis through the regulation of MEK/ERK and estrogen/ERα pathways. Thus, this work may define PKD1 as a novel potential anti-tumor therapeutic target.

A qualidade do ar nas áreas urbanas tende a apresentar concentrações indesejáveis de contaminantes provenientes da queima de biomassa, não havendo um sistema abrangente de monitoramento. Achados in vivo mostram que o diesel pode conter compostos que modulam a atividade do estrógeno. Estudos in vitro apoiam essa ideia, como o estudo realizado com cloreto de metileno extraído do diesel que comprova atuar como ativadores de ligação para os receptores de estrógeno. Esse trabalho tem por objetivo avaliar o efeito da exposição à metais presentes nas partículas de exaustao de diesel (PED) na morfologia do ovaário através da histologia, e análise do padrão de expressão dos receptores de estrógeno (ERs) no ovário de zebrafish (Danio rerio) usando a metodologia de PCR em tempo real. Fêmeas adultas de zebrafish foram expostas à concentrações ambientais de combinado de metais (Ni = 0,181 mg/L ; Fe = 0,07455 mg/L ; Pb= 0,05 mg/ L; Cd = 0,029 mg/ L; Cr = 0,161 mg/L ; Cu = 0,017 mg / L) por 3 dias. Em relação a contagem de ovócitos atrésicos a média observada nos animais expostos foi de 1,5 ± 0,4 e nos controles foi de 1,34 ± 0,3. Contudo, não houve diferença significativa entre os grupos (p > 0,05). Na expressão dos três genes receptores de estrógeno (esr1, esr2a, esr2b) as médias foram: 0,68; 1,32; 0,54; respectivamente. No entanto, não houve alteração significativa na expressão desses genes em relação aos controles. Os elementos traços presentes nas PED em concentração ambiental e em exposição aguda na fase adulta não alteram a expressão dos ERs o também não afetam o número de folículos atrésicos nos ovários / The air quality in urban areas tends to have undesirable concentrations of contaminants from biomass combustion, without a monitoring system. In vivo findings show that diesel may contain compounds that modulate the activity of estrogen. In vitro studies support this idea, as the study with methylene chloride extract from diesel proves that this substance act as activators binding to the estrogen receptors (ERs). This study aims to evaluate the effect of exposure to metals present in diesel exhaust particles (PED) in ovary morphology through histology, and analysis of expression pattern of ERs in ovary of zebrafish (Danio rerio) using real time PCR metodology. Adult females were exposed to ambient concentrations of combined metals (Ni = 0.181 mg / L, Fe = 0.07455 mg / L Pb = 0,05 mg / L; Cd = 0.029 mg / L; = 0.161 mg Cr / L, Cu = 0.017 mg / L) for 3 days. The mean of atretic oocytes counting observed in animals exposed was 1.5 ± 0.4 and the controls was 1.34 ± 0.3. However, no significant difference between groups was observed (p> 0.05). The expression of the three genes estrogen receptor (esr1, esr2a, esr2b) mean were: 0.68, 1.32, 0.54, respectively. However, no significant change in the expression of these genes in relation to controls was observed. In conclusion, the trace elements present in the PED concentration in environmental and acute exposure in adulthood not alter the expression of ERs and does not affect the number of atretic follicles in the ovary

Ensaios clínicos observacionais e em animais sugerem que o estrógeno exerça proteção cardiovascular, entretanto existem controvérsias mesmo após estudos randomizados. Tem sido sugerido que existe uma janela de oportunidade terapêutica, teoria timing hypothesis, que analisa o tratamento com estrógeno, iniciado precoce ou tardiamente, em mulheres na pós-menopausa. Avaliamos a função de carótidas de camundongos fêmeas com senescência acelerada (SAMP8) ou resistentes (SAMR1) ovariectomizadas tratadas com estrógeno precoce e tardiamente. Em SAMR1 os tratamentos promoveram vasculoproteção e nas carótidas das SAMP8 o tratamento com início precoce não alterou o efeito da ovariectomia, porém o tratamento com início tardio aumentou a vasoconstrição à fenilefrina, a produção de tromboxano (TXA2) e a expressão proteica do ERα-36kDa, splicing alternativo do receptor clássico ERα-66kDa. Portanto, os efeitos do estrógeno não foram benéficos no envelhecimento, podendo contribuir para o desenvolvimento de doenças cerebrovasculares decorrentes de alteração na circulação cerebral. / Observational clinical trials and animal studies demonstrated that estrogen promote cardiovascular protection. However, there are controversies after randomized clinical trials. It has been suggested that there is a therapeutic window of opportunity timing hypothesis theory , which analyzes the early and late estrogen treatments in postmenopausal women. We evaluated the carotid function in ovariectomized senescence (SAMP8) and resistant (SAMR1) female mice treated with estrogen in mineral oil solution dose of 5 g/kg by subcutaneous injection every three days. In SAMR1 estrogen treatments promoted vasculoprotection. In SAMP8 early-onset estrogen treatment did not change the effect observed in the ovariectomy, however late-onset estrogen treatment increased the vasoconstriction to phenylephrine, the thromboxane production and the protein expression of ERα-36kDa, alternative splicing. Therefore, the effects of estrogen were not beneficial in aging, contributing to the development of cardio and cerebrovascular diseases due to alteration cerebral circulation.

MyD88 est une protéine adaptatrice clé dans la signalisation des TLRs/IL-1R qui mène à l'activation de NF-KB et des MAPK, et à la production de cytokines inflammatoires. MyD88 participe à la tumorigénèse par le biais de son activité inflammatoire dans la signalisation des TLRs/IL-1R, et également via son interaction directe avec la kinase Erk dans la cellule cancéreuse. Dans cette thèse, nous identifions de nouveaux partenaires protéiques de MyD88 et nous examinons comment leurs interactions peuvent réguler sa fonction. Nous démontrons que MyD88 interagit avec Ubc9, ce qui conduit à sa sumoylation, et que cette modification posttraductionnelle régule négativement l'inflammation dépendante de MyD88. Nos résultats montrent également que MyD88 interagit avec le récepteur nucléaire, ER-α, et que cette interaction est nécessaire pour la réponse inflammatoire. Enfin, nous avons étudié l'importance de l'interaction MyD88/Erk dans le maintien de la transformation des tumeurs dépendant de l'oncogène Ras. Ces résultats pourraient éventuellement être exploités pour cibler MyD88 et ses interactions dans le traitement des maladies inflammatoires et le cancer / MyD88 is a protein that is at the interface between inflammation and cancer. It is the key adaptor protein used by TLRs/IL-1R to mediate their downstream signaling, resulting in NF-κB and MAPK activation, and inflammatory cytokine production. MyD88 also plays a role in tumorigenesis via two mechanisms, an inflammatory one dependent on its function in TLRs/IL- 1R signaling, and an intrinsic, cell-autonomous mechanism mediated by its interaction with the kinase Erk. Based on the different roles played by MyD88, this thesis work consisted in studying how MyD88 protein-protein interactions can regulate its function. We show that MyD88 interacts with Ubc9, resulting in its sumoylation and subsequent negative regulation of MyD88- mediated inflammation. We also demonstrate that MyD88 interacts with the nuclear receptor ER-α, an interaction necessary for the inflammatory response. Finally, we have studied the importance of the MyD88/Erk interaction in the maintenance of the transformed phenotype of Ras-dependent tumors. These findings could eventually be exploited to target MyD88 and its interactions in the treatment of inflammatory disorders and cancer

No description available.

Introdução: A endometriose é uma doença ginecológica comum caracterizada pela presença de estroma e/ou glândula endometrial fora da cavidade uterina, e que não possui sua etiopatogenia bem estabelecida. A transição epitélio-mesênquima (TEM) é um processo que consiste em uma série de mudanças no fenótipo de células epiteliais que fazem com que estas células assumam características de células mesenquimais. Assim como observado na TEM, as células endometriais no contexto da endometriose apresentam capacidade migratória, invasibilidade e elevada resistência à apoptose. As moléculas de adesão têm adquirido crescente relevância na TEM, pois relacionam-se à perda de adesão célula-célula com o aumento da invasão e metástase. O objetivo deste estudo foi investigar a expressão de marcadores relacionados com a TEM na endometriose superficial, ovariana e profunda. Pacientes e Métodos: Foram selecionadas 103 mulheres que preenchiam os critérios de inclusão estabelecidos, constituindo 2 grupos de estudo independentes entre si: 18 mulheres com endometriose peritoneal, ovariana e profunda concomitantes; 85 mulheres com endometriose ovariana e/ou profunda, dividido em 44 mulheres com endometriose ovariana e 41 com endometriose intestinal. Através de reações de imunoistoquímica, a expressão proteica dos marcadores e-caderina, n-caderina, betacatenina, receptor de estrogênio e receptor de progesterona foram avaliados nos tecidos de interesse em cada grupo de estudo. Além dos locais de doença, as mulheres foram avaliadas quanto à relação com a fase do ciclo e à classificação histológica da doença. Resultados: As lesões de endometriose de ovário mostraram uma menor expressão de n-caderina em comparação às lesões de intestino e peritônio (p=0,032). O receptor de estrogênio e receptor de progesterona se mostraram significativamente menos expressos no componente epitelial da doença de ovário do que no epitélio da endometriose de peritônio e intestino (p=0,002; p=0,48). A expressão da n-caderina apresentou uma correlação direta com a expressão do receptor de estrogênio no estroma da endometriose de intestino (p=0,036). Conclusão: Estes resultados sugerem que a transição epitélio-mesênquima esteja envolvida na etiopatogenia da endometriose, demonstrando que a doença de ovário se comporta de maneira diferente da doença superficial e da doença infiltrativa profunda, sendo a n-caderina um importante fator envolvido neste processo possivelmente influenciada pela ação do estrogênio / Background: Endometriosis is a common gynecological disease defined as the presence of ectopic endometrial glands and stroma outside the uterine cavity, and its pathogenesis is not well established. The epithelial to mesenchymal transition (EMT) is a process consisting of a series of changes in the phenotype of epithelial cells that make these cells assume the characteristics of mesenchymal cells. As observed in the EMT, endometrial cells in the context of endometriosis have the capacity of migration, invasiveness and high resistance to apoptosis. . The adhesion molecules have become progressively relevant in EMT, in view of the cell-to-cell adhesion loss, with increased invasion and metastasis. The goal of this study was to investigate the expression of markers related to EMT in superficial, ovarian and deep endometriosis. Patients and Methods: 103 women were selected who met the inclusion criteria, constituting two independent study groups: 18 women with peritoneal, ovarian and deep concomitant endometriosis, 85 women with ovarian and / or deep endometriosis, divided in 44 women with ovarian endometriosis and 41 with intestinal endometriosis. Through immunohistochemical reactions, the protein expression of e-cadherin, ncadherin, beta-catenin, estrogen receptor and progesterone receptor markers were evaluated in tissues of interest in each study group. In addition to the sites of the disease, menstrual phase and histological classification (well-differentiated, undifferentiated, mixed pattern and stromal) of the disease were recorded. Results: The ovarian endometrisis showed less n-cadherin marker than lesions of the peritoneum and bowel (p=0,032). Ovarian endometriosis also showed markedly decreased expression of estrogen and progesterone receptors in epithelial cells, compared with peritoneal and deep endometriosis (p=0,002; p=0,48). The expression of N-cadherin showed a direct correlation with estrogen receptor expression in the stroma of bowel endometriosis (p = 0.036). Conclusion: These results suggest that epithelial to mesenchymal transition involved in the pathogenesis of endometriosis, demonstrating that the ovary disease behaves differently disease than peritoneal and deep disease, so that the n-cadherin is an important factor involved in this process, possibly influenced by the action of estrogen

Les travaux épidémiologiques et expérimentaux effectués à ce jour sur le cancer du sein ont montré que les oestrogènes - comme l’eostradiole (E2) - et leur récépteur (ER) - un facteur de transcription les liants - sont fortement impliqués dans au moins 70% des cas de cancer du sein. Cette implication est d’autant plus visible que les patients, suite à une thérapie anti-oestrogénique, ont tendance à développer une résistance endocrinienne au traitement. Pendant longtemps, l’ER a été étudié en tant que facteur indépendant liant directement une séquence ADN spécifique sur le génome. Aujourd’hui le paradigme a profondément changé. Il est bien connu que ER s’associe avec de nombreux autres facteurs de transcription et protéines régulant la chromatine afin de réguler l’expression des gènes. Cependant, nos connaissances concernant la fonction de modifications épigénétiques suite à l’activation de ER - notamment la méthylation de l’ADN et l’acétylation des histones - sont encore limitées. Dans cette étude, j’ai mis en place un protocole de culture cellulaire adapté à l’étude de la privation et à la re-stimulation d’E2 stricto sensu. Dans un premier temps, ce protocole a été évalué à l’aide de la toute dernière technologie de puce permettant la lecture du méthylome et couvrant la liste complète des éléments amplificateurs. Dans un deuxième temps, j’ai mesuré le transcriptome et les profiles d’acétylation de l’histone H3 (H3K27ac) afin de déterminer la capacité de ER à réguler l’expression des gènes J’ai découvert que, suite à la privation de E2, les niveaux de méthylation de l’ADN et de H3K27ac changent et que ces changements s’accentuent avec le temps, en particulier au niveau des éléments amplificateurs. Une analyse d’enrichissement des facteurs de transcription et des séquences de liaison spécifiques a révélé que les facteurs de transcriptions des familles AP-1 et FOX sont des intermédiaires favorisants la liaison de ER aux éléments amplificateurs. Finalement, la re-stimulation des cellules par de l’E2 a montré que la majorité des changements épigénétiques observé sont réversibles mais que certains éléments amplificateurs restent hyperméthylés et déacétylés. Ceci pourrait indiquer que les traitements anti-oestrogéniques sont efficaces mais pourrait également indiquer un marqueur de résistance endocrinienne. Cette étude apporte des informations nouvelles quant aux effets de l’inhibition et l’activation de ER sur la méthylation de l’ADN et l’acétylation de l’histone H3 à l’échelle du génome et renforce l’importance du rôle d’autres facteurs au niveau des amplificateurs / Previous epidemiological and experimental studies have strongly implicated estrogens in breast cancer risk and Estrogen Receptor (ER), the transcription factor to which estrogen binds, is considered as the major molecular driver of around 70% breast cancers. The importance of the deregulated estrogen signalling is further highlighted by increasing evidence that current chemopreventive and therapeutic strategies that target hormonally responsive breast cancers frequently result in the development of resistance to anti-estrogens and metastatic progression, highlighting the need for understanding the molecular underlying mechanisms. While until recently, ER was believed to act as a stand-alone transcription factor, which can directly bind its motifs in DNA, it is now accepted that ER activity is a complex and dynamic process that requires highly concerted actions of a dozen transcriptional cofactors and various chromatin regulators at DNA. Recent studies focused on characterising ER-associated cofactors and their role in opening the chromatin provided a remarkable insight into transcriptional regulation mediated by ER. However DNA methylation and histone acetylation are poorly understood in the context of ER’s dynamic binding. In this thesis, I combined a cell culture protocol adapted for studying estradiol (E2) deprivation and re-stimulation in stricto sensu in ER-positive breast cancer cells with the latest methylation array, that allowed a genome-wide interrogation of DNA methylation (including a comprehensive panel of enhancers). I further investigated histone acetylation (ChIP-seq) and transcriptome (RNA-seq) after E2 deprivation and re-stimulation to better characterise the ability of ER to coordinate gene regulation. I found that E2 deprivation and re-stimulation result in time-dependent DNA methylation changes and in histone acetylation across diverse genomic regions, many of which overlap with enhancers. Further enrichment analysis of transcription factor (TF) binding and motif occurrence highlights the importance of ER tethering mainly through two partner TF families, AP-1 and FOX, in the proximity of enhancers that are differentially methylated and acetylated. This is the first study that comprehensively characterized DNA methylation at enhancers in response to inhibition and activation of ER signalling. The transcriptome and genome occupancy data further reinforced the notion that ER activity may orchestrate a broad transcriptional programme through regulating a limited panel of critical enhancers. Finally, the E2 re-stimulation experiments revealed that although the majority of the observed epigenetic changes induced by E2 deprivation could be largely reversed when the cells were re-stimulated we show that DNA hypermethylation and H3K27 acetylation at enhancers as well as several gene expression changes are selectively retained. The partial reversibility can be interpreted as a sign of treatment efficiency but also as a mechanism by which ER activity may contribute to endocrine resistance. This study provides entirely new information that constitutes a major advance in our understanding of the events by which ER and its cofactors mediate changes in DNA methylation and chromatin states at enhancers. These findings should open new avenues for studying role of the deregulated estrogen signalling in the mechanism underlying the “roots” of endocrine resistance that commonly develops in response to anti-estrogen therapy

The incidence of breast cancer became the most common female cancer, and the fourth cause of female cancer death. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF/MS) have been combined with multivariate statistics to investigate breast cancer tissues and cell lines. Core needle biopsy and fine needle aspiration (FNA) are techniques largely applied in the diagnosis of breast cancer. In this study, we have established an efficient protocol for detecting breast tissue and FNA samples with MALDI-TOF/MS. With the help of statistical analysis software, we can find the lipid-derived ion signals which can be use to distinguish breast cancer tumor tissues from non-tumor parts. This strategy can differentiate normal and tumor tissue, which is potential to apply in clinical diagnoses. The analysis of breast cancer tissue is challenging as the complexity of the tissue sample. Direct tissue analyses by matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) allows us to investigate the molecular structure and their distribution while maintaining the integrity of the tissue and avoiding the loss of signals from extraction steps. Combined MALDI-IMS with statistic software, tissues can be analyzed and classified based on their molecular content which is helpful to distinguish tumor regions from non-tumor regions of breast cancer tissue. Our result shows the differences in the distribution and content of lipids between tumor and non-tumor tissue which can be supplements of current pathological analysis in tumor margins. In this study, MALDI-TOF/MS combined with multivariate statistics were used to rapidly differentiate breast cancer cell lines with different estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) status. The protocol for efficiently detecting peptides and proteins in breast cancer cells with MALDI-TOF/MS was established, two multivariate statistics including principle component analysis (PCA) and hierarchical clustering analysis were used to process the obtaining MALDI mass spectra of six different breast cancer cell lines and one normal breast cell lines. Based on the difference of the peptide and protein profiles, breast cancer cell lines with same ER and HER-2 status were grouped in nearby region on the PCA score plot. The results of hierarchical cluster analysis also revealed high conformity between breast cancer cell protein profiles and respective hormone receptor types.

ABSTRACT MICROARRAY APPLICATIONS FOR DETERMINATION OF THE EFFECTS OF EMODIN ON BREAST CANCER CELL LINES Ekenel Qomi, Emilia M.S., Department of Biotechnology Supervisor: Prof. Dr. Mesude Iscan Co-Supervisor: Assoc. Prof. Dr. Nursen &Ccedil / oruh February 2012, 191 pages Cancer is a genetic disease that is characterized by uncontrolled cells growth. Breast cancer is a type of cancer originating from breast tissue. Some breast cancers are sensitive to hormones such as estrogen which makes it possible to treat them by blocking the effects of these hormones in the target tissues. These require less aggressive treatment than hormone negative cancers. Breast cancers without hormone receptors, are higher-risk, and are treated more aggressively. The aim of our study is to investigate the effect of emodin on MCF-7 which is ER (estrogen receptor) positive, and MDA-MB-231 (ER negative) cancerous cell lines. Emodin which is a phytoestrogen component, extracted from rheum (genus) plant, has been reported to suppress the growth of tumor in some clinical situation, and it&rsquo / s found that emodin induced apoptosis through the decrease of Bcl-2/Bax ratio and the increase of cytoplasm cytochrome c concentration in human breast cancer Bcap-37 cells. Comparing the effect of emodin between ER positive and ER negative cells at the molecular level was investigated by Microarray analysis of gene expressions using Affymetrix Human Genome U133 plus 2.0 Array. The microarray data analysis was performed by using BRB-Array Tools, v.4.2.0. GST and its classes / Alpha, Mu, Pi, Theta, Sigma, Omega, Zeta and Kappa is our interested genes because of its role in regulating susceptibility to cancer, by their ability to metabolize reactive electrophilic intermediates to usually less reactive and more water soluble glutathione conjugates. And also its have a role in detoxifying the damage caused by oxidative stress which is a result of the radiotherapy. v The differentially expressed genes from emodin treated and untreated control breast cancer cell lines were compared after normalization and filtering and annotated, it was shown that the top 10 highly (significantly) varied genes belong to the biological processes such as (namely) cell cycle, cell division, cell proliferation, mitosis and meiosis, this insure the relation of emodin to the cell growth processes in the cancerous cells. The analysis of the change on the cell growth confirmed the anti-tumor effect of emodin. About the effect of emodin treatment on MCF-7 and MDA-MB-231 cancerous cell lines separately / Both cells its significant genes was belong to cell growth biological processes, in MCF-7 cells in-addition other biological processes was shown, for example / stimulus to estradoil response, and the metabolism of xenobiotic by cytochrome p450, so CYP1A1 gene code for a protein which is used in emodin metabolism. The varied gene number was nearly 4400 gene from the scatter plot result in MCF-7 cells while in MDA-MB-231 cells it was nearly 3400 gene, these result insured the effect of emodin as a phytoestrogenic component as MCF-7 cells are ER positive cells, so emodin bind to the ER in MCF-7 cells and affected more gene number than MDA-MB-231. More number of GST enzyme classes changed in MCF-7 cells than MDA-MB-231, and the effect of emodin as anti-cancer showed different change of GST genes between MCF-7 and MDA-MB-231. The results confirmed by network analysis done, to find the most related genes to our top 10 regulated gene list, and these genes were analyzed / most of them where in our gene list, and their regulation after emodin treatment analyzed and the result was supported to emodin as anti-tumor and phytoestrogenic component.