Fas/FasL System in c-Myc Expressing Mammary Carcinoma Cells

摘要

PNCK, a novel pregnancy upregulated CaM kinase is upregulated in the mouse mammary gland during pregnancy, particularly in late pregnancy when alveolar epithelial cells exit the cell cycle and differentiate. PNCK is also upregulated in cultured over- confluent and serum-starved cells compared to actively growing mammary epithelial cells, suggesting that PNCK expression is inversely related to proliferation. Interestingly, PNCK is expressed in a subset of human breast tumor samples, but not in adjacent normal breast tissue. In mouse mammary carcinoma cell lines derived from MMTV-c-Myc driven tumors, PNCK expression is prominent, while no association is found between PNCK and MMTV- neu or MMTV-ras tumors. Recently, our lab discovered that a prominent survival pathway incident from the EGFR required calcium and calmodulin for the activation of Akt and the inhibition of c-Nyc mediated apoptosis in c-Nyc overexpressing mammary carcinoma cells. We hypothesize that PNCK (a calcium and calmodulin dependent protein) opposes the Akt activation properties of CaM in c- Nyc overexpressing cells and in mammary carcinoma cells in general. We successfully cloned and expressed the human PNCK transiently in epithelial cells. Our aim to functionally characterize PNCK in stable mammary carcinoma cells has been prevented by technical problems. We will now focus on optimizing a transient model of PNCK expression to uncover its function in mammary carcinoma cells.