Expression of retroviral sequences and oncogenes in rat liver tumors induced by diethylnitrosamine.

The expression of three cellular oncogenes (c-myc, c-Ha-ras, and c-delta-raf), the epidermal growth factor receptor gene, and two endogenous retrovirus-like sequences [rat leukemia virus (RaLV) and 30S] was examined in control rat livers and in 16 liver tumors. The tumors were induced in Sprague-Dawley male and female rats by a single i.p. injection of diethylnitrosamine at 1 or 2 days after birth, followed by dietary exposure to phenobarbital beginning at weaning. Increased expression of c-myc was seen in most of the tumors, but there was no consistent increase or decrease in expression of c-Ha-ras or c-delta-raf. It is of interest that a number of the tumor samples showed a decrease in epidermal growth factor receptor RNA. In all of the tumors, including both hepatocellular adenomas and carcinomas, there was a marked increase in expression of the endogenous RaLV sequence, and over 90% of the tumors displayed increased expression of the 30S endogenous retroviral-like sequence. No or a very low level of expression of the RaLV and 30S sequences was found in the control livers. The extent of expression of the RaLV and 30S sequences in individual tumors did not correlate with the extent of expression of c-myc or c-Ha-ras. Although increased expression of certain endogenous retrovirus-related sequences appears to be a common finding during rat liver carcinogenesis, the significance of this finding remains to be determined.