Sakairi T, Kobayashi K, Goto K, Okada M, Kusakabe M, Tsuchiya T, Sugimoto J, Sano F, Mutai M
Toxicology Laboratory, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., Kisarazu, Chiba, Japan.
Toxicol Pathol. 2001 Jul-Aug;29(4):479-82. doi: 10.1080/01926230152499962.
Transforming growth factor alpha (TGF-alpha) is a potent stimulator of normal hepatocyte proliferation, considered to have relationship to the liver regeneration or carcinogenesis. In this study, we investigated immunohistochemically the association between expression of TGF-alpha and cell proliferation activity in mouse hepatoblastomas (HBs) and hepatocellular carcinomas (HCCs) induced in B6C3F1 mice by diethylnitrosamine and sodium phenobarbital. The TGF-alpha-positive rate in HBs (29.2%) was significantly higher than that in HCCs (12.7%). Likewise, the proliferating cell nuclear antigen-positive rate (22.2%) was higher than the HCC value (14.5%). On the individual data for both TGF-alpha and PCNA, most of the HBs showed higher positive rates than HCCs. In HBs, TGF-alpha was localized only in the nuclei, whereas some HCC cells stained positive both in their nuclei and cytoplasm (0.6%). These results suggest expression of TGF-alpha and its localization might be linked to cell proliferation and play a role in malignant progression of mouse HBs.
转化生长因子α(TGF-α)是正常肝细胞增殖的强效刺激因子,被认为与肝脏再生或癌变有关。在本研究中,我们采用免疫组织化学方法,研究了二乙基亚硝胺和苯巴比妥钠诱导的B6C3F1小鼠肝母细胞瘤(HBs)和肝细胞癌(HCCs)中TGF-α表达与细胞增殖活性之间的关联。HBs中的TGF-α阳性率(29.2%)显著高于HCCs中的阳性率(12.7%)。同样,增殖细胞核抗原阳性率(22.2%)也高于HCC的数值(14.5%)。根据TGF-α和PCNA的个体数据,大多数HBs的阳性率高于HCCs。在HBs中,TGF-α仅定位于细胞核,而一些HCC细胞的细胞核和细胞质均呈阳性染色(0.6%)。这些结果表明,TGF-α的表达及其定位可能与细胞增殖相关,并在小鼠HBs的恶性进展中发挥作用。