Growth hormone modulates the expression of the β-galactoside-binding protein Galectin-1 in the liver

BACIGALUPO ML; PIAZZA VG; CICCONI N; CARABIAS P; OTERO S; BARTKE A; SOTELO AI; TRONCOSO MF; MIQUET JG

Ginebra

Congreso; European Association for the Study of the Liver (EASL) Hepatocellular carcinoma Summit; 2017

Background & aims: Growth hormone (GH) expression is associated with poor survival of hepatocellular carcinoma (HCC) patients. Transgenic mice overexpressing GH (GHTg) of 2-4 months old display a preneoplastic pathology similar to that present in humans at high risk of developing hepatic cancer, and old animals (11-14 months) frequently develop liver tumors. Galectin-1 (Gal1) is overexpressed in HCC patients, and is associated with low survival and poor prognosis. We reported that Gal1 overexpression in human HCC cells promotes tumor growth and metastasis in nude mice. Recently, a novel role of Gal1 in liver lipid accumulation after an hepatectomy was described. In this study we analyzed Gal1 expression in response to GH using in vivo and in vitro models.Methods: Gal1 expression was analyzed by immunoblotting, real time PCR and immunohistochemistry in the liver of GHTg mice (contain the bovine GH gene fused to control sequences of the rat phosphoenolpyruvate carboxykinase gene), and Swiss-Webster 3 week (w) old mice treated with GH (6 µg GH/ g body weight/ day) by implantation of osmotic pumps (continuous treatment) or by two daily injections (intermittent treatment) during 5 w. Human HCC HepG2 cells were treated with GH (1µg/ml) with or without the translation inhibitor cicloheximide (Cx, 10μM). Cells were scrapped and processed for immunoblotting at the indicated time. Results: Gal1 mRNA and protein expression levels were drastically upregulated in the liver of GHTg mice of 2 w (♀,♂n=8 p