The overall goal of this proposal is to gain a better understanding of the role of cyclin D family genes in cell cycle regulation, in particular during murine testicular cell development and differentiation. Of the known cell cycle regulators, cyclin D appears to play an important role in the G1/S transition. So far, three members of cyclin D family have been identified, cyclins D1, D2 and D3. Based on our preliminary data for the expression pattern of these genes in the mouse testis, we hypothesize that cyclin D1, D2 and D3 may play distinct roles during testicular cell development and differentiation. This proposal will begin to address these hypotheses by focusing on the following three specific aims: (1). To characterize the developmental expression of cyclin D1, D2 and D3 by immunohistochemistry and Western blot and the molecular structure of three different cyclin D3 transcripts in murine testicular cells by DNA library screening and sequencing; (2). To begin to determine which proteins interact with D-type cyclins during testicular cell development and differentiation by using immunoprecipitation an in vitro kinase assay; (3). To study the biological action of cyclin D1 and D3 during testicular cell development and differentiation by monitoring the effects of manipulating cyclin D1 and D3 in mouse testicular cells using transgenic approaches. Elucidating the function of D-type cyclins and in normal, partially transformed and tumorigenic states will greatly further our understanding of their role in both testicular cell development and differentiation, and the development of cancer.
