Inactivation of mouse tumor susceptibility gene tsg101 leads to neoplastic transformation which could reversed by restoration of tsg101 protein activity. In the varieties of human malignancies, no genomic defect could be identified questioning the role of TSG101as a classical tumor suppressor. Subsequent studies revealed presence of abnormal TSG101 transcripts in both tumor tissues and its normal counter parts, as well as in embryonic tissues. Hence, the relationship between TSG101 and human cancer development remains unclear. The previous studies have demonstrated that TSG101 has multiple biological functions, including regulations of protein degradation through ubiquitination, transcriptional, protein trafficking, cell survival and proliferation and epithelial cell differentiation. To further investigate the role of TSG101 in tumorigenesis, we employed immunohistochemistry and in situ hybridization analysis to study the expressions of TSG101 protein and mRNA in squamous cell carcinomas of different differentiation status. In addition, we scrutinized the relationship between TSG101 expression and the changs of cell cycle-related tumor suppressors and markers of epithelial differentiation, cell growth, tumor metastasis and apoptosis. The results reveal that TSG101 protein and mRNA are consistently expressed in the epidermal cells residing in the suprabasal, granular and cornified layers, but only weakly expressed in the cells of basal layer. The expressions of TSG101 are down regulated in poorly differentiated squamous cell carcinomas of various organs. Furthermore, TSG101 is also expressed in the tissue of squamous metaplasia, and the expression of TSG101 is positively related to that of cytokeratin. In addition, while TSG101 is down regulated, the expressions of p21Cip1/WAF1, p14ARF and MDM2 are also decreased ehereas that of p53 is conversely increased. Phospho-Rb and E-Cadherin were found to be down regulated in advanced cancers, but we failed to find their correlation with TSG101 on cell proliferation and tumor metastasis. Taken together, we hypothesize that TSG101 expression may influence and promote cell differentiation by regulating keratin expression, being involved in the MDM2-p53 circuit and interacting with p21Cip1/WAF1. Besides, by the integration of the studies of TSG101, keratin 10, and Rb protein expression, we infer that TSG101 may indirectly suppress expression of Rb by up-regulating keratin 10 in epithelial cells. The detailed mechanisms of the observation require further investigation. Nevertheless, our results have provided evidences to support the role of TSG101 on differentiation of squamous epithelial cells in addition to tumorigenesis.

No description available.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (doctoral)--Uppsala University, 1981. / At head of title: From the Department of Oncology, Division of Gynecologic Oncology, University Hospital, Uppsala, Sweden. Bibliography: p. 29-34.

Diss. med. dent. Zürich. / Literaturverz.

Diss. med. dent. Zürich. / Literaturverz.

Thesis (M.S.)--University of Missouri-Columbia, 2007. / "May 2007" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.

No description available.

Master of Science - Biology / á-catenin plays a crucial role in cell adhesion. Expression levels of á-catenin have been shown to be decreased in almost all tumours studied. The levels of the epidermal growth factor receptor (EGFR) were shown to be increased in oesophageal squamous cell carcinoma (OSCC) cell lines. á-catenin therefore, may play a part in linking the EGF pathway or other signal transduction pathways, bringing about some of the changes in the OSCC cell lines. The á-catenin gene from five OSCC cell lines was sequenced. Three out of five OSCC cell lines studied were found to harbour mutations. One of the mutations resulted in a change in the amino acid sequence of á-catenin. It was concluded that this alteration may not have affected the functioning of á-catenin. á-catenin was largely expressed at the plasma membrane with some weaker cytoplasm/nuclear expression occurring in all of the OSCC cell lines. Treatment of the OSCC cells with EGF for a 12 hour period resulted in no noticeable change in the expression levels of á- catenin. The results obtained from this study indicated that á-catenin could play a role in signal transduction pathways in the OSCC cell lines.