The Hcs7 Mouse Liver Cancer Modifier Maps to a 3.3 Mb Region Carrying the Strong Candidate Ifi202b

Bilger, Andrea; Poli, Elizabeth C.; Schneider, Andrew M.; Baus, Rebecca M.; Drinkwater, Norman R.

doi:10.5772/32529

Cited by 1 publication

(1 citation statement)

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“…The transcript showing the greatest (27-fold) dependence on Esr1 , Ifi202b , was previously shown to depend on Esr1 expression in splenic cells [ 34 ]. This gene carries a promoter mutation in the B6 strain that reduces its expression to approximately 2% of the expression in other strains [ 34 , 35 , 36 ]; Esr1 mutation reduces this expression further. None of the hepatic transcripts that varied in the LERKO animals was dependent on adult ovarian hormones.…”

Section: Resultsmentioning

confidence: 99%

Estrogen Receptor-α Suppresses Liver Carcinogenesis and Establishes Sex-Specific Gene Expression

O'Brien

Pitot

Chung

et al. 2021

Cancers

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Estrogen protects females from hepatocellular carcinoma (HCC). To determine whether this protection is mediated by classic estrogen receptors, we tested HCC susceptibility in estrogen receptor-deficient mice. In contrast to a previous study, we found that diethylnitrosamine induces hepatocarcinogenesis to a significantly greater extent when females lack Esr1, which encodes Estrogen Receptor-α. Relative to wild-type littermates, Esr1 knockout females developed 9-fold more tumors. Deficiency of Esr2, which encodes Estrogen Receptor-β, did not affect liver carcinogenesis in females. Using microarrays and QPCR to examine estrogen receptor effects on hepatic gene expression patterns, we found that germline Esr1 deficiency resulted in the masculinization of gene expression in the female liver. Six of the most dysregulated genes have previously been implicated in HCC. In contrast, Esr1 deletion specifically in hepatocytes of Esr1 conditional null female mice (in which Cre was expressed from the albumin promoter) resulted in the maintenance of female-specific liver gene expression. Wild-type adult females lacking ovarian estrogen due to ovariectomy, which is known to make females susceptible to HCC, also maintained female-specific expression in the liver of females. These studies indicate that Esr1 mediates liver cancer risk, and its control of sex-specific liver gene expression involves cells other than hepatocytes.

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