Estrogen exposure causes the progressive growth of SK-Hep1-derived tumor in ovariectomized mice.

Liver cancer, one of the leading death causes, has different incidence and mortality rates in men and women. The influencing factor is considered to estrogen. However, the role of estrogen in liver cancer remains controversial. In this study, we investigated the effects of estrogen on tumor progression. Total RNA sequencing was analyzed in SK-Hep1-derived tumor tissues, and 15 genes were expressed only in female mice. Among the differentially expressed genes, matrix metalloprotease 7 (MMP7), germ cell associated 1 (GSG1), and chromosome 6 open reading frame 15 (C6orf15) were associated with significantly different overall survival rates based on their expression level in liver cancer patients. Interestingly, exogenous estrogen aggravated SK-Hep1-derived tumor growth in ovariectomized (OVX) mice. When OVX mice were treated with exogenous estrogen, SK-Hep1-derived tumor tissues exhibited high MMP7 expression levels and low GSG1 and C6orf15 expression levels. These expression patterns were consistent with those of liver cancer patients with low overall survival rates. These results suggest that these genes are expected to be prognostic biomarkers of liver cancer. In conclusion, our results suggest that continuous estrogen exposure may promote tumor growth in OVX mice.