The impact of defective cholesterol metabolism on sex-specific hepatocarcinogenesis in hepatocyte specific deletion of Cyp51 in mice

The potential role of defective cholesterol metabolism in HCC development and exposition the Cyp51 gene as a promising marker with tumor suppressor potential in sex-dimorphic chronic liver pathogenesis in mice. Hepatocyte-specific Cyp51 knock-out (KO) and wild type (WT) mice on a mixed background (129/Pas (10%) × C57BL/6J (90%)) of both sexes (F and M) were investigated at the age of 24 months. From each of KO mice, two samples (a tumor and a surrounding tissue) were considered. Microarrays were hybridized with individual samples from livers of 14 mice (6 male, 8 female) at 24 months of age. 8 samples were hybridized from WT mice, i.e. 4 from male and 4 from female mice. 6 KO mice were investigated, i.e. 2 male and 4 female. From each of KO mice, two samples (a tumor and a surrounding tissue) were taken; altogether, 6 tumor and 6 corresponding surrounding-tissue samples were hybridized from KO mice.

本研究探讨了胆固醇代谢缺陷在肝细胞癌（Hepatocellular Carcinoma, HCC）发生发展中的潜在作用，并阐明了Cyp51基因作为小鼠性别二态性慢性肝脏发病机制中具备肿瘤抑制潜力的候选标志物的价值。实验对象为遗传背景为混合品系（129/Pas占10% × C57BL/6J占90%）的两性（雌性F、雄性M）肝细胞特异性Cyp51敲除（KO）与野生型（WT）小鼠，所有实验均在小鼠24月龄时开展。针对每只KO小鼠，预设采集肿瘤组织及其癌旁组织两份样本。本实验共对14只24月龄小鼠的肝脏个体样本进行基因芯片杂交：其中野生型小鼠样本共8份，雌雄各4份；敲除型小鼠共6只（雄性2只、雌性4只），每只采集肿瘤与癌旁组织样本，最终共获得6份肿瘤组织样本及6份配对癌旁组织样本用于芯片杂交。