Neoplastic transformation and lineage switching of rat liver epithelial cells by retrovirus-associated oncogenes.

Tumors produced by a chemically transformed rat liver epithelial (RLE) cell line and its single cell-derived clonal subpopulations demonstrate wide-ranging morphological presentations including carcinomas, sarcomas, "mixed epithelial-mesenchymal" tumors, and undifferentiated tumors [Am J Pathol 127:168-181, 1987]. To address the question of heterogeneity of tumors derived from transformed RLE cells, we have used recombinant retroviruses containing the following transforming oncogenes: v-raf (3611-MSV), v-raflv-myc (J2), v-myc (J5), and v-Ha-ras (pRNR16). All of the oncogenes, with the exception of v-myc (J5), were efficient transforming agents in the RLE cells. Tumors derived from the v-raf- and, to a lesser extent, those from v-Ha-ras-transformed RLE cells showed mixed epithelial-mesenchymal morphology, whereas the combination of v-raflv-myc (J2) consistently produced differentiated trabecular carcinomas. These data suggest that the lineage commitment of the RLE cells can be perturbed by a single transforming oncogene and that different tumor types derived from these cells may reflect the expression of a selective oncogene or a combination of oncogenes.