C—erbB2与乳腺癌三苯氧胺耐药细胞生长关系的研究

目的：探讨获得性三苯氧胺（TAM）抵抗乳腺癌细胞的生长调节途径及三苯氧胺（TAM）获得性抵抗的发生机制。方法：TAM诱导野生型人乳腺癌细胞系MCF-7/WT构建TAM抵抗的细胞系MCF-7／TAMR，RT—PCR、Westem blot及免疫细胞化学方法比较MCF-7／TAMR与MCF-7/WT细胞系中C—erbB2mRNA、蛋白表达及其活化状态的不同，用C—erbB2单克隆抗体herceptin对两种细胞系进行干预。观察细胞生长变化。结果：与MCF-7/WT细胞相比，MCF-7／TAMR细胞中cerbB-2的mRNA增加3倍（P〈0．05），蛋白增加1．5倍（P〈0．05）。Herceptin处理MCF-7／TAMR细胞，明显抑制了细胞的生长。结论：表皮生长因子受体特异性配体的自分泌释放作用可能通过CerbB-2／MAPK途径引起MCF-7／TAMR细胞的生长。

Study of Relationship between C-erbB2 and Tamoxifen-resistance in Breast Cancer

Objective： To study the growth regulation pathway of TAM-resistant breast cancer cell and the mechanism of required TAM-resistance（TAMR）. Methods： Wild-type MCF-7/WT was induced by TAM （=Tamoxifen） to construct MCF- 7/TAMR. RT-PCR,Western blot and immuocytochemical methods were used to detect the expression of C-erbB2 mRNA and protein in wild-type MCF-7 and in TAM-R MCF-7 cell line. Herceptin was used to inhibit the growth of the two cells. Results： Compared with wild-type MCF-7 cells, the mRNA of C-erbB2 increased 3 times with the protein 1.5 times higher in TAM-R MCF-7 cells. Treatment of TAM-R cells with Herceptin blocked c-erbB receptor and strongly inhibited cell growth. Conclusion： These results demonstrate that TAM-R MCF-7 cell growth is mediated by the autocrine release and C-erbB2/MAPK pathway may increase the growth of Tamoxifen-resistant cells.