TY - JOUR
T1 - 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
AU - Hällström, Inger Porsch
AU - Gustafsson, Jan Åke
AU - Blanck, Agneta
N1 - Funding Information:
This work was supported by grants from the National Cancer Institue (I RO1 CA42, 054-01A1). The Swedish Cancer Society, Cancerforeningen, Stockholm and the Research Funds of the Karolinska Institute.
PY - 1989/12
Y1 - 1989/12
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/10.12.2339
DO - 10.1093/carcin/10.12.2339
M3 - Article
C2 - 2480191
AN - SCOPUS:0024355572
SN - 0143-3334
VL - 10
SP - 2339
EP - 2343
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -