FGF-1和FGFR1在津白Ⅱ小鼠自发性乳腺癌发生中的作用

Effects of FGF-1 and FGFR1 on the Genesis of Spontaneous Breast Cancer in TA2 Mice

目的：比较TA2小鼠正常乳腺、乳腺癌前病变和乳腺癌组织中FGF-1和FGFRl的表达水平，初步探讨FGF-1及其受体FGFRl在TA2小鼠自发性乳腺癌发生中的作用及其机制。方法：收集正常TA2成年雌鼠的乳腺组织和TA2自发性乳腺癌雌鼠未成瘤的乳腺组织和乳腺癌组织，正常雌鼠乳腺经苏木素-伊红染色证实不存在不典型增生或癌变组织为正常乳腺组。共12例，TA2自发性乳腺癌雌鼠的未成瘤乳腺经苏木素-伊红染色证实为不典型增生组织为癌前病变组，发瘤小鼠的瘤组织经苏木素-伊红染色证实为乳腺癌的归为乳腺癌组，各17例；利用免疫组织化学方法测定各纽乳腺组织中FGF-1、PCNA、cyclinD1的表达量，并利用Real—timePCR方法测定各组织中FGF-1mRNA和FGFRlmRNA的表达量。结果：FGF-1mRNA和FGF-1蛋白在TA2自发性乳腺癌小鼠的癌前病变组织和乳腺癌组织中表达均高于正常乳腺（P均〈0．05），而癌前病变纽与乳腺癌组比较差异不具有统计学意义（D0．05）；FGFRlmRNA在TA2自发性乳腺癌小鼠的癌前病变组织和乳腺癌组织中表达均高于正常乳腺（P均〈0．05），同时FGFRl在癌前病变组织中的表达高于乳腺癌组织（P=0．046）；PCNA蛋白和cyclinDl蛋白在癌前病变组织和乳腺癌组织中表达也均高于正常乳腺（P均〈0．05），此外，cyclinDl在乳腺癌组织中的表达明显高于癌前病变组织（P=0．001）。结论：FGF-1和FGFRl可能参与了TA2小鼠自发性乳腺癌的发生，其作用的发挥可能是通过调节细胞周期促进细胞增殖而完成的。

Objective： To compare the expression of FGF-1 and FGFR1 in normal breast tissues, precan- cerous breast tissues and breast cancer tissues of TA2 mice, and to discuss the effect of FGF-1 and FGFR1 on the genesis of spontaneous breast cancer in TA2 mice. Methods： Normal breast tissues were obtained from normal TA2 female mice （12 cases）. Precancerous breast tissues and breast cancer tissues were obtained from TA2 female mice with spontaneous breast cancer （17 cases）. Immunohistochemistry was used to detect the expression of FGF-1, PCNA, and cyclin D1 proteins. Real time-PCR was employed to observe the expression of FGF-1 and FGFR1 mRNA. Results： The expression of FGF-1 mRNA and protein was higher in breast cancer and precancerous lesions than in the normal breast tissues （P〈0.05）. No significant difference was found in FGF-1 expression between breast cancer tissues and precancerous lesions （P〉0.05）. The expression of FGFR1 mRNA was higher in breast cancer tissues and precancerous lesions than in the normal breast tissues （P〈0.05）. A significant difference was found in FGFR1 mRNA expression between breast cancer tissues and precancerous lesions （P=0.046）. The expression of PCNA and cyclin D1 was higher in breast cancer tissues and precancerous lesions than in the normal breast tissues （P〈0.05）. The expression of cyclin D1 was higher in breast cancer tissues than in precancerous lesions （P=0.001）. Conclusion： FGF-1 and FGFR1 may contribute to the genesis of spontaneous breast cancer in TA2 mice by regulating cell cycle and promoting cell proliferation.