Transforming Growth Factor-α in Carcinogen- Induced F344 Rat Hepatic Foci
Transforming Growth Factor-α in Carcinogen- Induced F344 Rat Hepatic Foci
复制标题
致癌物诱导的 F344 大鼠肝病灶中的转化生长因子-α
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
J. Klaunig
中科院分区：
文献类型：
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作者：
K. Steinmetz;J. Klaunig
摘要转化生长因子-α（transforminggrowthfactor-α，TGF-α）是包括肝细胞在内的上皮细胞的正性生长调节因子。TGFα的过表达与人类和啮齿类动物终末期癌症的生长和恶性程度增加有关。本研究的总体目的是用苏木精和伊红（H和E）组织学表型表征二乙基亚硝胺诱导的雄性F344大鼠肝灶中的TGFα染色。还检查了个体局部DNA合成标记指数与TGFα存在之间的关联。肝病灶被确定为嗜酸性、嗜碱性、透明细胞或混合细胞。其中37.5%为TGFα标记阳性。TGFα在不同的H和E组织学表型之间的标记模式存在明显差异。在嗜酸性灶中观察到强烈、均匀的TGFα标记。嗜碱性灶标记为TGFα，在整个细胞质中弥漫均匀。在透明细胞病灶中，TGFα标记主要沿细胞膜的外周沿着发生。在混合细胞灶中，标记发生在沿着周边和弥漫性整个细胞质。在这些染色的载玻片上，谷胱甘肽-S-转移酶（胎盘; GSTP）在几乎所有嗜酸性和混合细胞灶中均被检测到，而大约一半的嗜碱性和透明细胞灶被GSTP染色。病灶中GSTP的存在并不总是与TGFα蛋白的增加相关。所有大鼠肝腺瘤和1例癌均标记为TGFα阳性。TGFα蛋白水平的升高与DNA合成标记指数的升高相关。DNA合成标记指数最高的TGFα阳性灶数显著高于DNA合成标记指数较低的TGF α阳性灶数。虽然TGFα的特征性染色模式与特定的组织学亚型相关，但TGFα在局灶性病变进展为瘤形成中的作用需要进一步定义。高水平的TGFα蛋白似乎是在肝癌发生过程中的某个时候获得的。获得高水平TGFα的早期病变可能是发展成肝细胞癌的病变（例如，肝细胞癌在致癌过程中很早就被确定）。显然，需要进一步的工作来阐明TGFα在啮齿动物和人类肝癌发生中的作用。
Abstract Transforming growth factor-α (TGFα) is a positive growth regulator in epithelial cells, including hepatocytes. Overexpression of TGFα has been associated with increased growth and malignancy of end-stage cancers in humans and rodents. The overall aim of this study was to characterize TGFα staining in diethylnitrosamine-induced hepatic foci from male F344 rats with the hematoxylin and eosin (H and E) histological phenotype. The association between the individual focal DNA synthesis labeling index and the presence of TGFα was also examined. Hepatic foci were identified as eosinophilic, basophilic, clear cell, or mixed cell. Of these foci, 37.5% labeled positive for TGFα. There were distinct differences in the pattern of TGFα labeling between the different H and E histological phenotypes. Intense, uniform TGFα labeling was observed in eosinophilic foci. Basophilic foci labeled for TGFα diffusely uniform throughout the cytoplasm. In clear-cell foci, TGFα labeling occurred primarily along the periphery of the cell membrane. In mixed-cell foci, labeling occurred both along the periphery and diffusely throughout the cytoplasm. On those slides stained, glutathione-S-transferase (placental; GSTP) was detected in almost all eosinophilic and mixed-cell foci, whereas approximately half of the basophilic and clear-cell foci stained for GSTP. The presence of GSTP in a focus was not always associated with the presence of increased TGFα protein. All rat hepatic adenomas and the one carcinoma labeled positive for TGFα. Increased levels of TGFα protein were associated with increased DNA synthesis labeling index. The number of TGFα-positive foci with the highest DNA synthesis labeling indices were statistically higher than those with lower levels of DNA synthesis labeling. Although characteristic staining patterns for TGFα were associated with specific histological subtype, the role that TGFα plays in the progression of focal lesions to neoplasia requires further definition. High levels of TGFα protein appear to be acquired sometime during the hepatocarcinogenic process. It may be that early lesions that acquire high levels of TGFα are the ones to develop into hepatocellular carcinoma (e.g., hepatocellular carcinoma is determined very early in the carcinogenic process). It is apparent that further work is needed to delineate the role of TGFα in both rodent and human hepatocarcinogenesis.