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Role of the Novel Kinase, H51, in Breast Development, Differentiation, and Carcinogenesis

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Several protein kinases involved in mammary gland development have been associated with human breast cancer and murine animal models of mammary gland carcinogenesis. To identify other protein kinases expressed in the mammary gland which may be involved in these processes, an RT-PCR degenerate oligonucleotide screen was performed on several transformed mammary epithelial cell lines and tissue derived from the mammary gland during different developmental stages. Forty-one kinases were identified, of which three were novel. One of these novel kinases, Krct, does not belong to any previously described subfamily of kinases. Analysis of the expression of murine Krct, demonstrates Krct expression in all tissues analyzed during all stages of development. Despite this wide expression pattern, Krct is preferentially expressed in the epithelium of several tissues including the mammary gland. Since many kinases regulate cellular proliferation and differentiation, it will be important to determine Krcts role in these processes. An analysis of the expression pattern of Krct during proliferation and differentiation has been initiated. Preliminary results demonstrated Krct mRNA levels may be cell cycle regulated. However, Krct protein levels in a serum starverefeed experiment remained constant. Therefore it is unclear if Krct is regulated in a cell cycle dependent fashion. Further analysis of Krct with proliferation and differentiation assays in vitro and in vivo will determine if Krct is involved in these cellular processes.

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Final rept. 1 Jul 1998-30 Jun 2001




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