P- 11 PROTUMORIGENIC GALECTINS 1 AND 3 ARE UPREGULATED IN THE LIVER OF MICE EXPOSED TO CONTINUOUS GROWTH HORMONE LEVELS

Introduction and Objectives

Human and animal evidence revealed a link between growth hormone (GH) and cancer risk. GH excess is implicated in rodent hepatocarcinogenesis. Transgenic mice overexpressing GH (GH-Tg) develop hepatocellular tumors at old ages, with preneoplastic liver pathology similar to that observed in humans at a high risk of developing hepatic cancer. Galectin 1 (GAL1) is involved in liver tumorigenesis in humans. We reported that GAL1 is upregulated in GH-Tg mice liver, even before histopathological alterations are detected, and particularly enhanced in liver tumors. This study aimed to evaluate if GH modulates the hepatic expression of GAL3, another protumorigenic galectin. As many proteins exhibit sexually dimorphic liver expression, mainly determined by distinct GH secretion patterns between males (intermittent) and females (more continuous), we assessed if GAL1 and GAL3 liver expression was affected by GH secretion patterns.

Materials and Methods

Hepatic GAL1 or GAL3 were analyzed by immunoblotting in GH-Tg mice exposed to continuously elevated GH levels and in Swiss-Webster mice treated with GH during five weeks by implantation of osmotic pumps (continuous treatment) or by two daily injections (intermittent treatment). Statistics: Student´s t-test or two-way ANOVA; P<0.05, significant; at least nine animals/experimental group.

Results

In GH-Tg mice (both sexes), GAL3 was not increased in the liver at early ages, when minimal histopathological alterations are found, but it was upregulated in young adults with preneoplastic livers and in older mice that develop liver tumors. However, GAL3 was not increased in tumors compared with the adjacent non-tumoral region. In Swiss-Webster mice, GAL1 and GAL3 expression were higher in females than in males. GH continuous treatment produced a significant increase in GAL1 and GAL3 expression in both sexes and loss of sexual dimorphism, while GH injections showed no effect.

Conclusions

GH continuous exposure upregulates protumorigenic GAL1 and GAL3 in mice liver. More studies are required to evaluate its impact on humans.