EFFECTS OF MUTATIONALLY ACTIVATED HA-RAS ON C-FOS EXPRESSION KINETICS IN RAT TRACHEAL EPITHELIAL CELLS

: The rat tracheal implant model was used to characterize the role of activated Ha-ras in the neoplastic progression of heterogeneous rat tracheal epithelial (RTE) cell populations. An activated Ha-ras-containing cell line, RTE 2-2, and its subclone, RTE 2-2n, which possesses only Ha-ras proto-oncogene alleles, were studied to determine whether activated ras could interact with the downstream signal transduction targets fos and myc and alter their cell-cycle-dependent expression in vitro. Transformed RTE cell lines with activated Ha-ras displayed earlier fos expression, with a peak at 15 min after serum stimulation. These cell lines also displayed a more accelerated loss of fos mRNA than seen in cells without activated Ha-ras. The effects on fos expression kinetics were seen only in cell lines with activated ras and were not related to the transformed phenotype of the cells. No change in myc expression kinetics were observed in any RTE cell line. These results suggest that mutations in ras can lead to alterations in nuclear components of the ras signaling pathway at the level of gene transcription.