Effects of growth hormone on the expression of c-myc and c-fos during early stages of sex-differentiated rat liver carcinogenesis in the resistant hepatocyte model.

The expression of the oncogenes c-myc and c-fos was studied in Wistar rats treated according to the resistant hepatocyte model. During early phases of promotion, i.e. the first 4 days after partial hepatectomy (PH) when the growth hormone (GH)-dependent sex difference in outgrowth of preneoplastic foci becomes manifest, c-myc and c-fos expression were compared in livers from males, females and GH-treated males. The expression of c-fos was almost doubled in males when compared to females 1 day after PH, a difference that gradually declined during the following days. In males receiving growth hormone in osmotic minipumps from 1 week after initiation the expression was at about the same level as that in females, c-myc expression was enhanced in males from the first day after PH and remained elevated, with a maximal 2.5-fold increase at day 2, while the expression in females and GH-treated males was practically unchanged. The increased c-myc expression in males and the effect of GH was still apparent 28 days after PH. Nuclear transcription assay showed a 2- to 3-fold higher transcription of the c-myc gene in untreated when compared with GH-treated males at the third day after PH. In conclusion, continuous GH infusion was shown to modulate the expression of c-myc and c-fos during the phase when sex-differentiated promotion is first observed. These findings might reflect a connection between the regulation of these genes and promotion of liver carcinogenesis. They might also be of possible importance for the understanding of the mechanism of hormone-related cancer.