INDUCTION OF MORPHOLOGICAL CHANGE BY TYROSINE KINASE INHIBITORS IN ROUS-SARCOMA VIRUS-TRANSFORMED RAT-KIDNEY CELLS

Erbstatin and methyl 2,5-dihydroxycinnamate, related tyrosine kinase inhibitors, induced a morphological change in temperature-sensitive Rous sarcoma virus-transformed rat kidney (RSV(ts)-NRK) that brought the cells close to the morphology of their normal counterpart. Erbstatin did not change the morphology of normal or Kirsten sarcoma virus-transformed rat kidney cells. Erbstatin also inhibited morphological transformation of RSV(ts)-NRK cells induced by a shifting in temperature. Actin stress fibres were observed only in normal cells and not in transformed cells. Erbstatin induced stress fibre organization in transformed cells. Erbstatin and methyl 2,5-dihydroxycinnamate increased fibronectin gene expression in RSV-transformed cells. Thus, tyrosine kinase inhibitors induced normal phenotypes specifically in v-src-expressing cells.