Inhibin/activin expression in human and rodent liver: Subunits α and Βb as new players in human hepatocellular carcinoma

Abstract

Background: Activins and inhibins belong to the TGFΒ-superfamily, which controls cell proliferation and differentiation in many organs. Activin A, the dimer of inhibin ΒA subunit, acts strongly anti-proliferative in hepatocytes. Little is known on the other activin/inhibin subunits in human liver and hepatocellular carcinoma (HCC). Methods: We studied the expression of the complete inhibin family α, ΒA, ΒB, ΒC, ΒE in normal liver, tumour-adjacent and HCC tissue, 12 additional organs and rodent liver. A total of 16 HCC and 10 disease-free livers were analysed. Expression of inhibin subunits was determined by qRT-PCR, normalised to RNA input and by geNorm algorithm, and confirmed by immunohistochemistry. Results: Remarkably, ΒA expression was not decreased in HCC. Similarly, ΒC and ΒE exhibited no major changes. In contrast, inhibin α, barely detectable in normal liver, was strongly increased in tumour-adjacent liver and dramatically enhanced in HCC. ΒB was strongly enhanced in some HCC. At variance with human liver, rodent liver showed higher inhibin α and ΒC expression, but ΒA was somewhat, and ΒB dramatically lower. Conclusions: Upregulation of inhibin α- and possibly of ΒB- may shield HCC cells from anti-proliferative effects of activin A. Dramatic variations between humans and rodents may reflect different functions of some inhibins/activins. © 2011 Cancer Research UK All rights reserved.