It is becoming clear that the mechanism of prostatic carcinogenesis and tumorigenesis is a multistep process involving a progression from pre-cancerous cells to cells which proliferate and metastasize and also a transformation from androgen-sensitive cancer to androgen-insensitive cancer. Understanding the molecular events driving the progression and transformation is critical to the early detection and method of treatment of prostate cancer. The proposed project is directed toward understanding whether and how oncogenetic events or other factors are involved in the progression and/or transformation of prostatic cancer cells. The role and function of androgen receptors in these processes will be explored. In addition, we will employ transgenic techniques to develop animal models that can be useful in the study of various aspects of prostate carcinogenesis and in the development of methods for the control of prostate cancer.
Specific Aims are: 1) To determine the interactions of androgen receptor with cytoplasmic/nuclear factors (proto-oncoproteins) which mediate the phenomenon of androgen-dependent cell proliferation in the LNCaP human prostate carcinoma cell line. 2) To determine the cellular events which cause the transition of prostate cancer cell proliferation from androgen-dependent to androgen-independent. 3) To initiate a program to set up a transgenic mouse model of prostate cancer for the purpose of identifying factors involved in the induction and progression of human prostate cancer. An understanding of causal factors and the existence of an experimental animal model would be useful for the development of new treatments for prostate cancer.
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