Thesis (Ph. D.)--University of Missouri--Columbia, 1996. / "December 1996." Typescript. Vita. Includes bibliographical references (leaves 196-206). Also available on the Internet.

Thesis (Ph. D.)--University of Missouri--Columbia, 1996. / Typescript. Vita. Includes bibliographical references (leaves: 196-206). Also available on the Internet.

No description available.

Breast cancer is the fifth most common cause of cancer death in the worldwide. In the past decades, tamoxifen has been used for clinical treatment for breast cancers. The derivatives of compound thiazolidinedione (TZDs) including troglitazone (rezulin) and rosiglitazone (avandia) are also in the stages of clinical trials. But in the earlier research, some studies reported that the use of these drugs was associated with some serious side effects. Cyclin D1 plays an important role in G1/S phase cell cycle progression and in growth factor- or estrogen-induced mammary epithelial cell proliferation. Cyclin D1 overexpression is also found in high percentage (over 30%) of human breast cancers, correlating with poor prognosis. In this study, we used a cyclin D1-ablative drug VGH No.47 to reduce the expression of cyclin D1 in human breast adenocarcinoma cell line MCF-7 (ER-positive) and MDA-MB-231 (ER-negative) and to study its effect on cell proliferation. Our results demonstrated that VGH No.47 decreased the protein stability of cyclin D1. Conversely, VGH No.47 reduced cyclin D1 at both transcriptional level and protein stability in ER-negative MDA-MB-231 cells. We found that VGH No.47 caused G2/M arrested in both breast cancer cell lines. In addition, we tested whether cyclin D1-ablative drug could sensitize breast cancer cells to tamoxifen and TZDs. We expect to lower the dose of tamoxifen, troglitazone or rosiglitazone to reduce the side effects, but the results do not meet our expectation and do not exhibit synergistic effect.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Adelaide, Dept. of Chemistry, 1999. / Bibliography: p. 143-160.

Thesis (Ph.D.)--University of Adelaide, Dept. of Molecular Biosciences, 2002. / "August 2002." Bibliography: p. 157-169.

Hamburg, University, Diss., 2003.

<p> PEA3 is a member of the expanding Ets family of transcription factors. In the adult mouse, pea3 mRNA is expressed at highest levels in the brain, epididymis and at lower levels in the mammary gland, testes, ovary and uterus. PEA3 is overexpressed in 93% of all HER2/Neu positive human breast tumors and in 77% of mouse multiple intestinal (Min) tumors. Many of these tumors have disruptions in the Ras/MAPK and Wnt signaling pathways. Analysis of the influence of these pathways on pea3 promoter activity revealed that effectors of both pathways increased transcription from this promoter. Deletion mutations of the pea3 promoter linked to a luciferase reporter gene were used to localize the DNA sequences that are responsible for the effect of the Ras/MAPK pathway on its expression. A Ras-responsive element (RRE), composed of an ETS and an AP-1 binding site, was identified between sequences -247 and -227 and its importance was confirmed through mutational analysis. </p> <p> CYCLIN Dl is a potent oncogene involved in different types of tumors. The CYCLIN D1 gene is amplified in 20% of human mammary carcinomas, and its mRNA is overexpressed in 50% of human breast cancers. The CYCLIN Dl (CDJ) promoter was shown to be responsive to PEA3 transactivation and to dominant-negative PEA3 inhibition in co-transfection experiments in Cos-1 cells. Of the 4 Ets-binding sites (EBS) in the CDJ promoter, one site was shown to be important for the activity of the promoter and for its capacity to respond to PEA3 transactivation. It was also determined that PEA3, ~-catenin, Lef-1 and c-Jun cooperated synergistically to activate the CDJ promoter. PEA3 was absolutely required for the manifestation of this synergy among these transcription factors. These findings collectively illustrate the key role of PEA3 as an effector of multiple oncogenic signaling pathways. </p> / Thesis / Master of Science (MSc)

Thesis (M.S.)--Duquesne University, 2009. / Title from document title page. Abstract included in electronic submission form. Includes bibliographical references (p. 106-112) and index.