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Expression of retroviral sequences and oncogenes in rat liver tumors induced by diethylnitrosamine
Abstract:
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.
Insights
Increased expression of rat leukemia virus (RaLV) and 30S retroviral sequences was observed in most chemically induced rat liver tumors. This finding suggests a potential role for these endogenous retroviral sequences in liver carcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Virology
Background:
- Chemical induction of rat liver tumors involves complex genetic alterations.
- Cellular oncogenes and growth factor receptors are frequently dysregulated during carcinogenesis.
Purpose of the Study:
- To investigate the expression patterns of specific oncogenes, growth factor receptor, and endogenous retroviral sequences in chemically induced rat liver tumors.
- To determine the correlation between the expression of these genes and retroviral sequences during liver carcinogenesis.
Main Methods:
- Diethylnitrosamine was used to induce liver tumors in Sprague-Dawley rats.
- Gene expression analysis was performed on control livers and tumor samples using techniques likely involving RNA detection (e.g., Northern blot, RT-PCR).
Main Results:
- Most tumors showed increased c-myc expression, while c-Ha-ras and c-delta-raf expression varied.
- Epidermal growth factor receptor RNA levels decreased in some tumors.
- A significant increase in rat leukemia virus (RaLV) and 30S endogenous retroviral-like sequences was observed in all tumors compared to control livers.
- No correlation was found between RaLV/30S expression and c-myc or c-Ha-ras expression levels.
Conclusions:
- Increased expression of endogenous retroviral-like sequences (RaLV and 30S) is a common event in rat liver carcinogenesis.
- The specific role and significance of these upregulated retroviral sequences in the carcinogenic process require further investigation.