Role of squamous cell carcinoma antigen-1 on liver cells after partial hepatectomy in transgenic mice

Abstract

Squamous Cell Carcinoma Antigen-1 (SCCA1) overexpression has been observed in tumours of epithelial origin and in hepatocellular carcinoma. Previous data indicate that this serpin inhibits apoptosis, while its proliferative activity was only recently proposed. The aim of this study was to evaluate the effect of SCCA1 on liver cells in a transgenic mouse model after partial hepatectomy. Twenty-one C57BL/6J mice (11 transgenic for human SCCA1, 10 wild-type) underwent partial hepatectomy and were sacrified after one week. Apoptosis and proliferation markers were determined in the liver at sacrifice, while a cytokine panel was measured in serum. Transgenic mice showed a relative liver weight significantly higher than wild-type mice at sacrifice (mean ±SD, 5.38±0.50% vs 4.84±0.29%, p=0.0221), while no difference (p=0.2403) was observed in two untreated control groups (6 transgenic, 6 wild-type mice). Active caspase-3 was significantly lower in transgenic mice than in wild-type mice (p=0.0047). The transgenic mouse group showed overall higher proliferative activity at sacrifice, compared to wild-type mice, with increased proliferation parameters. Cytokine analysis revealed a remarkable and opposite sex-dependent behaviour of interleukin (IL)-6 after hepatectomy. At variance with wild-type mice, a significant IL-6 increase was documented only in transgenic females (p=0.0313), even more relevant than that observed in wild-type males. In conclusion, transgenic mice expressing SCCA1 showed higher liver regenerative potential compared to wild-type mice, supporting the dual role of this serpin as an anti-apoptotic and pro-proliferative stimulus for liver cells in vivo.