Effects of signalling transduction modulators on the transformed phenotypes in v-H-ras-transformed NIH 3T3 cells

Several signalling transduction modulators were used to examine their effects on the morhpological changes, foci formation in soft agar and cellular growth in v-H-ras-transformed NIH 3T3 cells. The results from this study showed that specific tyrosine kinase inhibitors (genistein and tyrphostin 23) and cyclic AMP-elevating agents (forskolin and 3-isobutyl-1-methyl-xanthine) could effectively induce differential flat phenotype of v-H-ras transformant at micromolar concentrations. At the same dose range, both signalling modulators also caused a significant suppression of anchorage-independent and cellular growth in the same transformant. By contrast, compound inhibitors such as protein kinase C (staurosporin and H-7), phospholipase A₂ (aristolochic acid), phospholipase C (neomycin sulfate) and cyclooxygenase (indomathacin) all did not alter the cellular morphology or foci formation in soft agar, although PKC inhibitors exhibited a slight inhibition on the cellular growth. Based on these observations, we propose that the alterations of protein kinase A or tyrosine kinase-associated signal pathways is necessary and the original cause of the transformation event, but that increase of the activities of protein kinase C, phospholipase C, phospholipase A₂ or cyclooxygenase probably is an indirect result of the v-H-ras-mediated transformation.