RELATIONSHIP OF P215(BRCA1) TO TYROSINE KINASE SIGNALING PATHWAYS ANDTHE CELL-CYCLE IN NORMAL AND TRANSFORMED-CELLS

We have analysed the relationship of the products of two genes, neu an d BRCA1, known to be important in human breast cancer, Highly specific antibodies that recognized both the rodent and human form of the BRCA 1 gene product (M-r 215 kDa, p215(BRCA1)) were developed to facilitate these efforts, p215(BRCA1) was identified as a tyrosine phosphorylate d protein primarily localized in the nucleus of several breast cancer cell lines, In transformed murine and human cells, levels of p215(BRCA 1) tyrosine phosphorylation were inversely correlated with the activit y of the erbB family receptor-tyrosine-kinases and with the transforme d growth features of these cells, Regulation of p215(BRCA1) tyrosine p hosphorylation was also related to events in the cell cycle, Increased levels of p215(BRCA1) phosphotyrosine content were observed in NIH3T3 cells arrested at the G(2)/M transition, These findings indicate that the products of BRCA1, neu, and erbB breast cancer genes participate in a common or shared signaling pathway important in cell growth and i ts regulation.