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Expression of oncogenes during rat chemical hepatotumorigenesis promoted by estrogen
Y Himeno1, Y Fukuda, M Hatanaka
1Department of Internal Medicine, Faculty of Medicine, Kyoto University.
Abstract:
To elucidate the role of oncogene expression in hepatocarcinogenesis, we examined the expression of 4 cellular oncogenes (c-myc, c-fos, Ha-ras and c-erbA) in liver tissues induced by chemical agents. Four groups of male Sprague-Dawley rats were examined in the present study. Rats of the first and second groups were given a single intraperitoneal injection of diethylnitrosamine (DEN), 200 mg/kg body weight. Two weeks later, these rats were divided into two groups; the DEN-C group received no further medication, whereas the DEN-DES group was given diethylstilbestrol (DES), 0.5 mg/day, for 12 months. The DEN group was given DEN, 100 ppm, in drinking water for five months as the hepatocellular carcinoma (HCC) group. The DES group was given DES, 0.5 mg/day, from the start for 8 months. Rats of the DEN-DES and DEN groups developed grossly visible hepatic tumors. Significantly higher levels of c-myc gene expression were observed in tissues of HCC of the DEN group and in neoplastic nodules of the DEN-DES groups than in the DES and DEN-C group. The increase of c-myc mRNA seemed to begin after 1 month of treatment and became significant at 4 months in the DEN-DES group. On the other hand, no significant differences in mRNA levels of c-fos, Ha-ras and c-erbA were observed among these four groups. Although the significance of increased c-myc gene expression in neoplastic liver is still not known, it is conceivable that the persistent elevation of c-myc gene expression in the DEN and DEN-DES groups might contribute to the development of rat chemical hepatotumorigenesis.
Insights
This study investigated oncogene expression in chemically induced rat liver cancer. Results show elevated c-myc gene expression in tumors, suggesting its role in hepatocarcinogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Hepatology
Background:
- Hepatocellular carcinoma (HCC) development involves complex genetic alterations.
- Oncogene expression is a key factor in chemical carcinogenesis.
Purpose of the Study:
- To investigate the role of four cellular oncogenes (c-myc, c-fos, Ha-ras, c-erbA) in chemically induced hepatocarcinogenesis in rats.
- To correlate oncogene expression levels with tumor development.
Main Methods:
- Rats were exposed to diethylnitrosamine (DEN) and/or diethylstilbestrol (DES) to induce liver tumors.
- Gene expression of c-myc, c-fos, Ha-ras, and c-erbA was analyzed in liver tissues using mRNA levels.
- Tumor development was assessed grossly and histologically.
Main Results:
- Significantly higher c-myc gene expression was observed in hepatocellular carcinoma (HCC) tissues and neoplastic nodules compared to control groups.
- Elevated c-myc mRNA levels were detected as early as 1 month and became significant at 4 months post-treatment in the DEN-DES group.
- No significant differences in c-fos, Ha-ras, or c-erbA mRNA levels were found among the experimental groups.
Conclusions:
- Persistent elevation of c-myc gene expression may contribute to the development of chemically induced rat liver tumors.
- c-myc appears to play a critical role in hepatocarcinogenesis, while c-fos, Ha-ras, and c-erbA do not show significant changes in this model.
- Further research is needed to fully understand the significance of increased c-myc expression in neoplastic liver development.