Characteristics of Dehydroepiandrosterone-induced Hepatocarcinogenesis in the Rat
Dehydroepiandrosterone (DHEA) induces and enhances hepatocarcinogenesis in the rat, the tumor incidence being higher in females than in males. Preneoplastic and neoplastic lesions induced by DHEA belong to the amphophilic cell lineage of hepatocarcinogenesis. Moreover, DHEA modulates preneoplastic liver foci of the glycogenotic/basophilic cell lineage induced by the hepatocarcinogen N-nitrosomorpholine (NNM) to amphophilic cell foci (APF). This process is associated with profound changes in the expression of key enzymes of energy metabolism and a down-regulation of the expression of insulin receptor substrate-1, a signaling molecule activated by tyrosine kinase receptors, which is over-expressed in glycogenotic lesions. This suggests a cross-talk of the steroid-mediated signaling pathway with tyrosine kinase receptor-activated signal transduction pathways during enhancement of hepatocarcinogenesis by DHEA.
KeywordsGlycogen Content Peroxisome Proliferation Tumor Incidence Preneoplastic Lesion Cell Focus
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