The TRK and RET tyrosine kinase oncogenes cooperate with ras in the neoplastic transformation of a rat thyroid epithelial cell line.

We have recently reported that about 50% of papillary thyroid carcinomas harbor an activated TRK or RET oncogene. Two retroviral vectors containing the activated TRK or RET/PTC oncogene have been used to infect a differentiated rat thyroid epithelial cell line, namely the PC Clone 3 cell line. Upon infection with the TRK virus, the PC Clone 3 cells lost only the ability to trap iodide and to express the thyroperoxidase gene. Conversely, when infected with the PTC virus, the PC Clone 3 cells completely lost all of their differentiated functions. However, both the PC-TRK and PC-PTC cell lines were unable to grow in soft agar, and they were not tumorigenic when injected into nude mice. A completely undifferentiated and malignant phenotype was obtained by the cooperation between the TRK or RET and the viral Ha-ras or Ki-ras oncogenes.