BRK TYROSINE KINASE EXPRESSION IN A HIGH PROPORTION OF HUMAN BREAST CARCINOMAS

BRK is a recently described non receptor protein tyrosine kinase whose mRNA was found to be expressed in human breast tumours and breast can cer cell lines, Expression of BRK in fibroblasts and mammary epithelia l cells has been shown to enhance their ability to grow anchorage inde pendently, and mammary epithelial cells expressing BRK acquire a poten tiated mitogenic response to epidermal growth factor, In order to inve stigate further the expression of BRK in breast cancers, we have isola ted monoclonal antibodies specifically recognising the protein, Wherea s BRK expression was low or undetectable in normal mammary tissue and benign lesions, approximately two-thirds of breast tumours expressed a ppreciable levels, and 27% of tumours over expressed BRK by fivefold o r more (up to 43x), This expression pattern was mirrored in a comparis on of cell lines derived either from normal mammary epithelial cells o r from carcinomas, BRK expression was found to be constant throughout the cell cycle, and did not vary with cell proliferation rate, A consi deration of this expression data, in conjunction with BRK's demonstrat ed ability to deregulate the proliferation of mammary epithelial cells , supports the hypothesis that the over expression of BRK in a high pr oportion of breast carcinomas is a functionally important factor in th eir evolution.