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THE IDENTIFICATION OF NOVEL KINASE GENES ASSOCIATED WITH
ANDROGEN INDEPENDENT PROSTATE CANCER
by
Ayesha Bhatia
A Thesis Presented to the
FACULTY OF THE USC GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(MOLECULAR MICROBIOLOGY AND IMMUNOLOGY)
May 2010
Copyright 2010 Ayesha Bhatia
Object Description
| Title | The identification of novel kinase genes associated with androgen independent prostate cancer |
| Author | Bhatia, Ayesha |
| Author email | ayeshabh@usc.edu; ayeshabhatia@gmail.com |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Molecular Microbiology & Immunology |
| School | Keck School of Medicine |
| Date defended/completed | 2010-03-17 |
| Date submitted | 2010 |
| Restricted until | Restricted until 07 May. 2011. |
| Date published | 2011-05-07 |
| Advisor (committee chair) | Jung, Jae U. |
| Advisor (committee member) |
Coetzee, Gerhard A. Yuan, Weiming |
| Abstract | Prostate cancer is one of the most common forms of cancer in America affecting one in six men over the age of 65 (Greenlee et al., 2001). When confined to the prostate, surgical removal of the prostate may be curative but when it spreads beyond the prostate, treatment options include radiation, chemotherapy and hormone ablation therapy. The tumor cells initially regress but recur in a more aggressive and fatal form, which is resistant to androgen ablation therapy.; Several pathways, including the MAP kinase pathway have been implicated in the transition of prostate cancer from an androgen-dependent (AD) state to an androgen-depletion-independent (ADI) state. In clinical samples however, no mutations in the RASpathway components have been found (Weber et al., 2004). Hence, we attempted to identify novel kinase genes, which are potentially associated with androgen-depletion-independent (ADI) prostate cancer by screening a library containing 354 activated human kinases. Based on this screening we identified TPL2 as a novel kinase gene associated with ADI prostate cancer, which was functionally validated by gain-of-function and loss-of-function studies. ADI prostate cancer growth of cells in culture was also seen to diminish in response to a TPL2 kinase specific inhibitor. Finally, TPL2 is indeed overexpressed in ADI prostate cancer in tumor samples and cell lines derived from the PB-Cre/PTENf/f mouse model system, which shows a prostate specific homozygous deletion of PTEN, leading to prostate cancer development which is initially AD, but responds to castration and recurs later in an ADI form.; Hence, we identified TPL2 as a novel kinase gene associated with ADI prostate cancer, which can serve as a potential therapeutic target against ADI prostate cancer. |
| Keyword | prostate cancer; androgen-depletion-independent |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Provenance | Electronically uploaded by the author |
| Type | texts |
| Legacy record ID | usctheses-m3032 |
| Contributing entity | University of Southern California |
| Rights | Bhatia, Ayesha |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-Bhatia-3587 |
| Archival file | uscthesesreloadpub_Volume17/etd-Bhatia-3587.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | THE IDENTIFICATION OF NOVEL KINASE GENES ASSOCIATED WITH ANDROGEN INDEPENDENT PROSTATE CANCER by Ayesha Bhatia A Thesis Presented to the FACULTY OF THE USC GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (MOLECULAR MICROBIOLOGY AND IMMUNOLOGY) May 2010 Copyright 2010 Ayesha Bhatia |
