It remains to be shown whether ovarian estrogen protects adult female mice against HCC development via Esr1, since we did not see similar changes in the gene expression pattern after ovariectomy as with a germline mutation of Esr1. Six genes highly dysregulated in Esr1 KO mice have been implicated in HCC and may mediate the protection conferred by Esr1. The gene discussed is ESR1; the disease is hepatocellular carcinoma.