Quantitative relationship between transforming growth factor-alpha and hepatic focal phenotype and progression in female mouse liver
Quantitative relationship between transforming growth factor-alpha and hepatic focal phenotype and progression in female mouse liver
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DOI：
10.1177/019262339702500305
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发表时间：
1997-05-01
影响因子：
1.5
通讯作者：
Goldsworthy, TL
中科院分区：
文献类型：
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作者：
Moser, GJ;Wolf, DC;Goldsworthy, TL
在大鼠和人的肝脏肿瘤中，阳性的肝细胞生长因子-转化生长因子-α(转化生长因子-α)及其受体表皮生长因子受体(EGFR)的调节发生。本研究的目的是确定在DEN引发的小鼠暴露于各种肝癌诱因后，嗜碱性和嗜酸性癌前病变和肿瘤性病变中的转化生长因子-α和表皮生长因子受体是否发生改变。雌性B6C3F1小鼠用N-亚硝基二乙胺(DEN)致癌，并用不同浓度的无铅汽油蒸气(2000ppm)、甲基叔丁基醚蒸气(7814ppm)、苯巴比妥(500ppm，饲料)或氯丹(25ppm，饲料)治疗。用免疫组织化学方法检测肝组织中转化生长因子-α和表皮生长因子受体的表达。在所有治疗组中，嗜碱性肝病灶的转化生长因子-α免疫反应均为阴性(554/564，98%)。相反，无论采用何种治疗，嗜酸性肝病灶均呈转化生长因子-α免疫阳性(107/108，99%)。用5-溴-2‘-脱氧尿嘧啶核苷掺入法测定的平均肝标记指数在转化生长因子-α免疫阳性和非免疫阳性病灶之间无显著差异。在以嗜碱性表型为主的肝细胞肿瘤中，转化生长因子-α免疫反应的发生率增加。在嗜碱性肝细胞腺瘤中，有16/81(20%)呈阳性反应，而肝细胞癌中有17/29(59%)呈阳性反应。嗜碱性肝细胞腺瘤(17/67，25%)和癌(19/28，68%)的EGFR免疫反应阳性率高于嗜碱性病灶(11/367，3%)，提示小鼠肝肿瘤的发生是一种自分泌机制。嗜碱性肝肿瘤中转化生长因子-α免疫反应性增加，提示转化生长因子-α是小鼠肝脏肿瘤进展的标志。此外，转化生长因子-α的调节依赖于表型而不是治疗，这表明转化生长因子-α在嗜碱性和嗜酸性肝脏病变中的表达存在固有差异。
Modulations in the positive hepatocyte growth factor, transforming growth factor-alpha (TGF-alpha) and its receptor epidermal growth factor receptor (EGFR), occur in rat and human liver tumors. The purpose of this study was to determine if TGF-alpha and EGFR are altered in basophilic and acidophilic preneoplastic and neoplastic liver lesions generated in DEN-initiated mice exposed to a variety of hepatocarcinogens. Female B6C3F1 mice were initiated with N-nitrosodiethylamine (DEN) and treated with hepatocarcinogenic concentrations of unleaded gasoline vapor (2,000 ppm), methyl tertiary butyl ether vapor (7,814 ppm), phenobarbital (500 ppm, diet), or chlordane (25 ppm, diet). Hepatic foci and tumors were identified and evaluated immunohistochemically with antibodies for TGF-alpha and EGFR. In all treatment groups, basophilic hepatic foci were negative for TGF-alpha immunoreactivity (554/564, 98%). In contrast, regardless of treatment, acidophilic hepatic foci were immunoreactive for TGF-alpha (107/108, 99%). There was no significant difference in mean hepatic labeling index as measured by the incorporation of 5-bromo-2'-deoxyuridine between foci immunoreactive and nonimmunoreactive for TGF-alpha. The incidence of immunoreactivity for TGF-alpha increased in hepatocellular tumors that were predominantly of the basophilic phenotype. Of basophilic hepatocellular adenomas, 16/81 (20%) were immunoreactive for TGF-alpha, while 17/29 (59%) of hepatocellular carcinomas stained positive for TGF-alpha. A similar increased incidence of EGFR immunoreactivity was found in basophilic hepatocellular adenomas (17/67, 25%) and carcinomas (19/28, 68%) relative to basophilic foci (11/367, 3%), suggesting an autocrine mechanism for the development of mouse liver tumors. The increased incidence of TGF-alpha immunoreactivity in basophilic liver tumors suggests that TGF-alpha is a marker of tumor progression in mouse liver. Furthermore, TGF-alpha modulations were dependent on phenotype rather than treatment, indicating inherent differences in the expression of TGF-alpha in basophilic and acidophilic hepatic lesions.