Prostate cancer is the leading cause of male cancer-related deaths in the United States (about 32,000 this year) and the leading diagnosed cancer in American men (about 241,000 new cases in 2012). The number of new prostate cancer diagnoses has risen recently. These alarming statistics require special attention from clinicians, healthcare providers, scientific communities, and funding agencies. Different genetic changes have been identified to cause prostate cancer in men. One of the common mechanisms of tumor formation in cancer patients is inactivation of one or more so- called tumor suppressor genes. Inactivation of tumor suppressor genes has devastating consequences on the regulation of cell growth within a specific tissue and results in tumor development. Our group has identified one such tumor suppressor gene, Abi1/Hssh3bp1, and has developed a novel conditional knockout mouse model to study the role of this gene in development of prostate cancer. Prostate-specific disruption of the Abi1/Hssh3bp1 gene leads to development of prostatic intraepithelial neoplasia (PIN). Given our published data indicating that the observed prostate pathology in Abi1 KO mice is the result of abnormally regulated cell- to-cell adhesion and activation of PI-3 kinase-Akt pathway, this mouse model provides a much- needed mechanistically based animal model with which to conduct detailed studies of Abi1's tumor suppressive role as well as its role in the initiation of neoplastic processes leading to prostate cancer. Moreover, our preliminary data from additional mouse models generated in the lab indicate that Abi1 acts downstream from the most commonly mutated gene in prostate cancer, PTEN, and regulates tumor invasion. A better understanding of Abi1's function might lead to new therapeutic options for the treatment of prostate cancer and establishment of the novel mouse model for translational research in prostate cancer.

Public Health Relevance

Prostate cancer is the leading cause of cancer-related deaths in males in the United States and a leading diagnosed cancer in American men, with about 240,000 new cases in 2012. Here we propose to study mechanisms underlying prostate cancer by using a novel genetically engineered mouse model of prostate cancer produced in our laboratory. We hope that our research will lead to significant advancement of our basic knowledge, including identification of novel processes that lead to tumor formation and to identification of novel drug targets for cancer therapies.

National Institute of Health (NIH)
Research Project (R01)
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Tumor Cell Biology Study Section (TCB)
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Yassin, Rihab R,
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Upstate Medical University
Schools of Medicine
United States
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