OVEREXPRESSION OF THE FOCAL ADHESION KINASE (P125(FAK)) IN INVASIVE HUMAN TUMORS

The focal adhesion kinase (FAK) gene encodes a tyrosine kinase (p125(F AK)) thought to be involved in signal transduction pathways used in ce ll adhesion, motility, and anchorage-independent growth. Because alter ations in these cellular processes occur in tumor invasion and metasta sis, Ne studied the protein expression of FAK in a variety of human tu mors and found that in the 119 samples studied, increased levels of p1 25(FAK) correlated with the invasive potential of a tumor, By comparin g FAK expression in tumors with normal tissue from the same patient, w e found that p125(FAK) was significantly elevated in 17 (100%) of 17 i nvasive and metastatic colonic lesions and in 22 (88%) of 25 invasive and metastatic breast tumors, Additional studies of FAK expression in 13 high grade sarcomas showed high levels in ail samples compared to b enign, noninvasive mesenchymal specimens. Furthermore, FAK protein lev els were elevated in preinvasive lesions, such as large (>2 cm) coloni c villous adenomas, whereas noninvasive, yet hypercellular, neoplastic tissues such as parathyroid and hepatocellular adenomas did not overe xpress FAK, These data provide evidence that both epithelial and mesen chymal tumor progression are accompanied by increased p125(FAK) expres sion and suggest that the level of FAK. expression might be a marker f or the invasive potential of a tumor.