Secreted Pdz Domain-Containing Protein 2 (Spdzd2): A Potential Autocrine Tumor Suppressor Chun-Wai Tam audiobook

Secreted Pdz Domain-Containing Protein 2 (Spdzd2): A Potential Autocrine Tumor Suppressor Chun-Wai Tam audiobook

Secreted Pdz Domain-Containing Protein 2 (Spdzd2): A Potential Autocrine Tumor Suppressor Chun-Wai Tam audiobook free

This dissertation, "Secreted PDZ Domain-containing Protein 2 (sPDZD2): a Potential Autocrine Tumor Suppressor" by Chun-wai, Tam, 談振偉, 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 Secreted PDZ domain-containing protein 2 (sPDZD2): A potential autocrine tumor suppressor Submitted by Chun Wai TAM for the degree of Doctor of Philosophy at The University of Hong Kong in May 2007 Cancer is a global public health problem. In 2002, 10. 9 million new cancer cases and 6. 7 million cancer deaths were reported worldwide. This huge disease burden has fueled research on novel endo- /para- /autocrine growth-promoting and growth-inhibitory signaling pathways important in cancer pathogenesis. PDZ domain-containing protein 2 (PDZD2), a multi-PDZ protein expressed in many mammalian tissues, has been reported previously to be increased in human prostate cancer tissues, suggesting that it may play a role in tumorigenesis. Besides, PDZD2 is cleaved by a caspase-dependent mechanism to form a secreted PDZ domain-containing protein 2 (sPDZD2) with unknown functions in humans. In this study, endogenous expression of PDZD2 and secretion of sPDZD2 were detected in human prostate cancer LNCaP, DU145, PC-3 and 22Rv1 cells, immortalized prostate epithelial cells RWPE-1, breast cancer MCF-7 and MDA-MB-468 cells, as well as liver cancer Hep-G2 and Hep-3B cells. Inhibition of endogenous sPDZD2 production and secretion by DU145, PC-3, 22Rv1, RWPE-1, MCF-7 and Hep-G2 cells via the specific caspase-3 inhibitor Z-DEVD-FMK resulted in increased cell proliferation, which could be abrogated by treatment with exogenous purified recombinant sPDZD2. Recombinant sPDZD2 protein induced anti-proliferative effects on prostate cancer DU145, PC-3 and 22Rv1 cells, breast cancer MCF-7 and liver cancer Hep-G2 cells, as well as apoptotic effects on LNCaP cells, in a concentration dependent manner. The apoptotic effects of sPDZD2 on LNCaP cells were apparently mediated via p53-independent Bad stimulation, whereas the anti-proliferative effects of sPDZD2 on prostate cancer PC-3 and 22Rv1 cells were possibly mediated by p53-independent mechanisms. In contrast, sPDZD2 induced cellular senescence of prostate cancer DU145 cells, as well as anti-proliferation on breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. In DU145 cells, CIP1/WAF1 upregulation of p21 protein expression was also observed. Furthermore, sPDZD2 sensitized mutant p53-positive prostate cancer DU145 cells and wild-type p53-positive breast cancer MCF-7 cells to apoptosis induction through genotoxic (DNA-damage) stress imposed by sub-lethal concentration of hydrogen peroxide. Together, the present study demonstrated that sPDZD2 protein is a novel autocrine ligand which can exert tumor-suppressive effects on different types of cancers via stimulation of p53 gene and protein expression. (353 words) DOI: 10. 5353/th_b3955737 Subjects: AntioncogenesCancer cells - GrowthApoptosisProstate - Cancer - Genetic aspects.

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Secreted Pdz Domain-Containing Protein 2 (Spdzd2): A Potential Autocrine Tumor Suppressor Chun-Wai Tam audio book download

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  • Language: English
  • ISBN-10: 1374667617
  • ISBN-13: 978-1374667617
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  • Weight: 1.5 pounds
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