Tumor-promoting/progressing role of additional chromosome instability in hepatic carcinogenesis in Sgo1 (Shugoshin 1) haploinsufficient mice

Carcinogenesis
Hiroshi Y YamadaChinthalapally V Rao

Abstract

A major etiological risk factor for hepatocellular carcinoma (HCC) is infection by Hepatitis viruses, especially hepatitis B virus and hepatitis C virus. Hepatitis B virus and hepatitis C virus do not cause aggressive activation of an oncogenic pathway, but they transactivate a broad array of genes, cause chronic inflammation, and, through interference with mitotic processes, lead to mitotic error-induced chromosome instability (ME-CIN). However, how ME-CIN is involved in the development of HCC remains unclear. Delineating the effect of ME-CIN on HCC development should help in identifying measures to combat HCC. In this study, we used ME-CIN model mice haploinsufficient in Shugoshin 1 (Sgo1(-/+)) to assess the role of ME-CIN in HCC development. Treatment with the carcinogen azoxymethane caused Sgo1(-/+) ME-CIN model mice to develop HCCs within 6 months, whereas control mice developed no HCC (P < 0.003). The HCC development was associated with expression of early HCC markers (glutamine synthetase, glypican 3, heat shock protein 70, and the serum marker alpha fetoprotein), although without fibrosis. ME-CIN preceded the expression of HCC markers, suggesting that ME-CIN is an important early event in HCC development. In 12-month-ol...Continue Reading

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Citations

Aug 18, 2016·Molecular Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
Nov 14, 2016·Carcinogenesis·Chinthalapally V RaoHiroshi Y Yamada
Oct 3, 2019·Experimental Biology and Medicine·Shirley Jusino, Harold I Saavedra
Sep 14, 2019·Cell Cycle·Jessica PichéGregor Andelfinger
Jun 3, 2021·Cancers·Chinthalapally V RaoHiroshi Y Yamada

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