TYROSINE PHOSPHORYLATION AS A MARKER FOR ABERRANTLY REGULATED GROWTH-PROMOTING PATHWAYS IN CELL-LINES DERIVED FROM HEAD AND NECK MALIGNANCIES

We have utilized a broad approach to address whether tyrosine kinases and the growth pathways they regulate might be functionally aberrant i n squamous cell carcinomas (SCC) of the upper aerodigestive tract. Thi s strategy involved assaying for evidence of tyrosine kinase action in lysates of cell lines representing SCC. Our findings revealed a spect rum of elevated tyrosine phosphorylation in SCC lines ranging from les s than 2-fold to more than 10-fold above that of control human epiderm al keratinocytes. Thus the ability to regulate growth and other pathwa ys controlled by tyrosine phosphorylation was impaired in all the 19 l ines examined. Assessment of the receptor for epidermal growth factor (EGF) revealed that its activity was elevated above normal in 14 of th e 19 cell lines examined, suggesting that at least a portion of the in creased tyrosine phosphorylation observed could be attributed to exces sive EGF receptor activity. Our findings provide functional evidence t hat growth pathways are aberrantly regulated in cell lines representin g SCC of the upper aerodigestive tract. (C) 1995 Wiley-Liss, Inc.