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Growth Hormone-Regulated Expression of the c-myc Gene during Sex-Differentiated Promotion of Rat Liver Carcinogenesis

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Abstract

The expression of the c-myc gene was analysed in livers from male, female and growth hormone (GH)-treated male Wistar rats during selection/promotion with two sex-differentiated promoters of liver cancer. During the period after partial hepatectomy (PH) in the “resistant hepatocyte (RH) model”, when the growth of the putatively “preneoplastic” lesions is markedly faster in males than in females and males “feminized” by continuous GH infusion, a significantly increased c-myc expression was observed in males. A maximal increase (2.5 fold) was observed 2 days post PH, and the expression was still elevated 4 weeks after the operation. No increase was observed in females and GH-treated males. An increased nuclear transcription of the c-myc gene was observed 3 days post PH when compared with the PH level in untreated but not in GH-treated males.

After 5 weeks of treatment with dietary deoxycholic acid (DCA) detectable levels of hepatic foci were observed only in males. one week after the PH performed at 5 weeks foci areas in males exihibited a 2-fold increase. Foci areas in liver from females and GH-treated males were detectable but 2–3 fold smaller than in ordinary males. The c-myc expression increased approximately 2-fold in all groups following 5 weeks of DCA treatment, with the highest expression observed in males. The expression was further increased in response to PH. GH treatment of males almost completely “feminized” both focal growth and c-myc expression.

In conclusion, we have observed a correlation between GH-regulated sex differences in focal growth and the expression of the c-myc gene, possibly implicating a role for the regulation of this gene is sex-differentiated promotion of liver cancer.

A manuscript containing parts of the data presented here has been published in Carcinogenesis 10: 2339 (1989).

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© 1991 Springer Science+Business Media New York

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Hällström, I.P., Blanck, A. (1991). Growth Hormone-Regulated Expression of the c-myc Gene during Sex-Differentiated Promotion of Rat Liver Carcinogenesis. In: Columbano, A., Feo, F., Pascale, R., Pani, P. (eds) Chemical Carcinogenesis 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3694-9_9

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  • DOI: https://doi.org/10.1007/978-1-4615-3694-9_9

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6642-3

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