Kitano Mitsuaki, Wada Jutaro, Ariki Yutaka, Kato Masanori, Wanibuchi Hideki, Morimura Keiichirou, Hidaka Takayoshi, Hosoe Kazunori, Fukushima Shoji
First Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Osaka 545-8585, Japan.
Cancer Sci. 2006 Jun;97(6):478-83. doi: 10.1111/j.1349-7006.2006.00210.x.
Expression of TGF-alpha during promotion of neoplastic development from GST-P-positive foci in rat chemical hepatocarcinogenesis was investigated. One-hundred male F344 rats were given a single intraperitoneal injection of DEN (200 mg/kg bodyweight) and subjected to two-thirds partial hepatectomy at week 3. Commencing 2 weeks from the start, PB at doses of 0 or 500 p.p.m. was fed to the rats for 46 weeks. Groups of 10 rats were killed at weeks 4, 8, 16, 32, 48 and their livers were immunohistochemically examined for expression of GST-P and TGF-alpha. TGF-alpha-positive foci and single positive cells were observed from week 4, partially overlapping with GST-P-positive foci but being much fewer. Numbers of TGF-alpha-positive lesions did not increase from weeks 4-48, but their areas showed increment at weeks 32 and 48, especially with PB administration. Almost all of the tumors observed at weeks 16, 32 and 48 were positive for TGF-alpha (98%). In addition, epidermal growth factor receptor overexpression was observed in most TGF-alpha-positive lesions (foci and tumors). The proliferating cell nuclear antigen labeling index in double positive foci for GST-P and TGF-alpha was significantly higher than that in TGF-alpha-negative foci. In conclusion, TGF-alpha may be closely related with promotion from altered foci to neoplasms in rat hepatocarcinogenesis. Our data suggest that double positive foci for GST-P and TGF-alpha in the early stages of rat hepatocarcinogenesis may develop into tumors with promotion.
研究了在大鼠化学性肝癌发生过程中，从谷胱甘肽S-转移酶胎盘型（GST-P）阳性灶促进肿瘤发展期间转化生长因子α（TGF-α）的表达。100只雄性F344大鼠腹腔注射一次二乙基亚硝胺（DEN，200mg/kg体重），并在第3周进行三分之二肝部分切除术。从开始后的第2周起，以0或500ppm的剂量给大鼠喂食苯巴比妥（PB），持续46周。在第4、8、16、32、48周处死每组10只大鼠，对其肝脏进行免疫组织化学检查，以检测GST-P和TGF-α的表达。从第4周开始观察到TGF-α阳性灶和单个阳性细胞，它们与GST-P阳性灶部分重叠，但数量少得多。TGF-α阳性病变的数量在第4至48周没有增加，但其面积在第32周和48周有所增加，尤其是在给予PB的情况下。在第16、32和48周观察到的几乎所有肿瘤TGF-α均呈阳性（98%）。此外，在大多数TGF-α阳性病变（灶和肿瘤）中观察到表皮生长因子受体过表达。GST-P和TGF-α双阳性灶中的增殖细胞核抗原标记指数显著高于TGF-α阴性灶。总之，在大鼠肝癌发生过程中，TGF-α可能与从改变的病灶向肿瘤的促进密切相关。我们的数据表明，大鼠肝癌发生早期GST-P和TGF-α双阳性灶可能在促进作用下发展为肿瘤。
