There is strong evidence that polypeptide growth factors such as transforming growth factor (TGFa), epidermal growth factor (EGF), and fibroblast growth factor (FGF) are involved in regulation of the growth of normal as well as abnormal prostate cells. Most of these growth factors mediate their signals through receptor-tyrosine kinases. Tyrosine kinases, while representing a minor population of protein kinases in the cell, play major roles in cellular growth, differentiation and apoptosis. Surprisingly, little is known about the tyrosine kinases expressed in prostate tissues and the growth signals they transmit. Built upon a significant amount of preliminary data, the investigator's experiences in receptor-tyrosine kinase and the coinvestigator's expertise in prostate organ culture, this application is intended to provide fundamental knowledge on the growth signals and tyrosine kinases expressed in normal and abnormal prostate cells. We have recently developed an effective approach to profile tyrosine kinases in a given cell, which has allowed us to describe most, if not all, of the tyrosine kinases in a prostate carcinoma. We wish to apply this approach to study and contrast the tyrosine kinase patterns in normal and abnormal prostate cells. One of the major aims is to identify novel and tissue-specific kinases in prostate tissues.
A second aim i s to use erbB/EGF receptor as a paradigm to study the crucial signal pathways involved in growth regulation of normal prostate cells. The """"""""cross-talk"""""""" between cytokine receptor and growth factor receptor will also be explored.
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