Reversal of transformed phenotypes by herbimycin A in src oncogene expressed rat fibroblasts

Abstract

We studied the effectiveness of herbimycin A, an inhibitor of the function of the src oncogene, to reverse the various transformed phenotypes in normal rat kidney (NRK) cells integrating temperature-sensitive v-src (ts/NRK). Elevated glucose transport in ts/NRK cells at a permissive temperature (33 degrees C) was decreased by herbimycin in 8 h to near the level that was observed either in ts/NRK grown at a nonpermissive temperature (39 degrees C) or in untransformed NRK cells at either temperature. Herbimycin caused no significant decrease in glucose uptake in ts/NRK cells grown at 39 degrees C. The effects of herbimycin on serum- and anchorage-independent growth properties of ts/NRK cells and of NRK cells integrating K-ras (KNRK) were also examined. With ts/NRK cells grown at 33 degrees C, the inhibition of cell growth by herbimycin became more pronounced when the serum concentration in the medium was lowered. With KNRK cells, in contrast, almost the same extent of cell growth inhibition was exerted by herbimycin irrespective of the serum concentration. Furthermore, with ts/NRK cells grown at 33 degrees C, herbimycin inhibited the colony formation in the soft agar medium more strongly than on a solid support. No such differential effects were observed with KNRK cells under similar conditions. These results suggest that herbimycin specifically acts on cells expressing the src oncogene and reverses various transformed characteristics to the normal ones.