Protein Kinases in Human Breast Carcinoma
Annual rept. 1 Jul 1999-30 Jun 2000
NORTH CAROLINA UNIV AT CHAPEL HILL
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This project focuses on the biology of the Rak protein tyrosine kinase in human breast cancer. Rak is a 54 kDa protein tyrosine kinase expressed in epithelial cells. Rak resembles the proto-oncogene Src structurally, but Rak lacks an amino-terminal myristylation site and localizes to the nuclear and perinuclear regions of the cell. We report here that expression of Rak in breast cancer cells inhibits growth and causes G1 arrest of the cell cycle. This growth inhibition is kinase-dependent, but does not require the Rak SH2 or SH3 domains. Rak also binds to the pRb retinoblastoma tumor suppressor protein, but Rak inhibits growth even in cells that lack pRb. These results ar consistent with Rak functioning as a regulator of cell growth that is distinct from the Src-related kinase family. Our other studies are examining the expression of Rak in human breast cancer specimens using monoclonal antibodies as well as Taqman analysis of mRNA expression. We are also producing an adenoviral Rak construct to allow robust expression of Rak in breast cancer cells to further assess the growth inhibitory effect and to characterize the biology of this growth inhibitory protein tyrosine kinase.
- Medicine and Medical Research