Go to  Advanced Search

The role of BIRC6, a member of the inhibitor of apoptosis protein (IAP) family, in the survival of human prostate cancer cells

Show full item record

Files in this item

Files Size Format Description   View
ubc_2010_fall_low_christopher.pdf 2.356Mb Adobe Portable Document Format   View/Open
 
Title: The role of BIRC6, a member of the inhibitor of apoptosis protein (IAP) family, in the survival of human prostate cancer cells
Author: Low, Christopher Gah-Mun
Degree Master of Science - MSc
Program Interdisciplinary Oncology
Copyright Date: 2010
Publicly Available in cIRcle 2011-10-31
Abstract: Prostate cancer is the most commonly diagnosed cancer and third leading cause of cancer deaths in Canadian men. Prostate cancers typically begin as androgen-dependent tumours susceptible to growth arrest/apoptosis induced by ablation of androgens. Although initially effective, androgen ablation frequently leads to the development of castration-resistant (androgen-independent) prostate cancer, which is generally also resistant to other available treatments. Development of castration-resistant prostate cancer is characteristically associated with marked increases in resistance to apoptosis. BIRC6 is a member of the Inhibitors of Apoptosis Protein (IAP) family which protects a variety of cancer cell lines from apoptosis. In the present study, we have investigated whether BIRC6 plays a role in prostate cancer and could potentially be useful as a novel therapeutic target. Analysis of a variety of human prostate cancer cell lines and clinical specimens for BIRC6 protein expression, using Western blot and immunohistochemical analyses, respectively, showed that BIRC6 protein is markedly expressed by the prostate cancer cell lines and by clinical cancer specimens, as distinct from benign prostate cells/tissue. In addition, analysis of the clinical specimens showed that elevated BIRC6 protein expression was found to be particularly associated with cancers of Gleason score 6-8 and with the development of castration-resistant disease. Specific, siRNA-induced reduction of BIRC6 expression in LNCaP cells led to a marked reduction in cell proliferation, associated with an increase in apoptosis markers and a decrease in autophagosome markers, indicating that BIRC6 plays a major protective role in the proliferation of LNCaP cells by inhibiting apoptosis and perhaps by enhancing autophagy. Taken together, the data suggest an important role for BIRC6 in prostate cancer growth and progression, particularly, in the development of treatment resistance. In conclusion, this study indicates - for the first time - that the BIRC6 gene and its product are potentially valuable targets for therapy of human prostate cancers. BIRC6-targeting drugs may be especially useful for sensitization of cancer cells in combination therapy.
URI: http://hdl.handle.net/2429/29564
Scholarly Level: Graduate

This item appears in the following Collection(s)

Show full item record

All items in cIRcle are protected by copyright, with all rights reserved.

Attribution-NonCommercial 2.5 Canada Except where otherwise noted, this item's license is described as Attribution-NonCommercial 2.5 Canada

UBC Library
1961 East Mall
Vancouver, B.C.
Canada V6T 1Z1
Tel: 604-822-6375
Fax: 604-822-3893