Regulation of Cadherins and Catenins in Ovarian Surface Epithelium and Ovarian Cancer
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Regulation of Cadherins and Catenins in Ovarian Surface Epithelium and Ovarian Cancer

Regulation of Cadherins and Catenins in Ovarian Surface Epithelium and Ovarian Cancer


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About the Book

This dissertation, "Regulation of Cadherins and Catenins in Ovarian Surface Epithelium and Ovarian Cancer" by Yuen-lam, Pon, 潘婉琳, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled REGULATION OF CADHERINS AND CATENINS IN OVARIAN SURFACE EPITHELIUM AND OVARIAN CANCER Submitted by PON Yuen Lam For the degree of Doctor of Philosophy at The University of Hong Kong in Dec 2007 Cadherins and catenins, in addition to acting as structural adhesion molecules, also function as modulators of gene activities. They are subjected to dynamic changes under tight regulation in ovarian surface epithelium (OSE) and ovarian cancer cells and are involved in the modulation of cell survival, apoptosis, and migration/invasion. The objective of this study is to examine the regulation of cadherins and catenins in OSE and ovarian cancer, in relation to their functions in normal physiology and pathological progression. These results demonstrated that gonadotropins played a major role in controlling OSE survival and that this function was mediated via the regulation of N-cadherin through a cAMP/protein kinase A signaling pathway by both post-translational and transcriptional mechanisms. It was shown that the downregulation of N-cadherin by gonadotropins resulted in a redistribution of β-catenin from the plasma membrane to the cytosol/nucleus, where β-catenin activated T-cell factor (TCF)-dependent transcription of target genes such as cyclooxygenase-2. The participation of β-catenin in adhesion and signaling may represent a novel mechanism through which gonadotropins may regulate the cellular fate of human OSE. By using microarray analysis, I identified a number of novel genes that may be implicated in the apoptotic function of β-catenin in OSE. Some of them are not yet annotated as direct or indirect targets of β-catenin, and thus may represent new function(s) of β-catenin. Finally, cell-cell adhesion has also been implicated to be of great importance for the invasive capacity of tumor cells. I have recently demonstrated that p70 S6 kinase (p70s6k) as a critical regulator of ovarian cancer invasion and migration. Here I presented evidence suggesting that this tumorigenic activity of p70s6k was associated with the ability of p70s6k to repress E-cadherin through the upregulation of the Snail transcription factor. The induction of Snail was caused by two complementary effects: ubiquitin-proteasome degradation and gene transcription. Preliminary data was shown that p70s6K might be important in development using a zebrafish model. Taken together, these findings suggest that cadherins and catenins play an important role in OSE and ovarian cancer. Understanding their mechanism of action and regulation will be important to ovarian cancer for future development of novel approaches for diagnosis and treatment of this deadly disease. DOI: 10.5353/th_b3963423 Subjects: Cadherins Epithelium Ovaries - Cancer - Genetic aspects


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Product Details
  • ISBN-13: 9781374676237
  • Publisher: Open Dissertation Press
  • Publisher Imprint: Open Dissertation Press
  • Edition: Annotated edition
  • Language: English
  • Spine Width: 13 mm
  • Width: 216 mm
  • ISBN-10: 1374676233
  • Publisher Date: 27 Jan 2017
  • Binding: Hardback
  • Height: 279 mm
  • No of Pages: 212
  • Weight: 780 gr

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