乳腺癌细胞株的转化生长因子-β生长抑制反应与转化生长因子-β受体基因改变的相关性

Correlation between growth inhibitory responses of TGF-β and genetic change of TGF-β receptor in human breast cancer cell lines

目的 :研究转化生长因子 - β( TGF- β)对人乳腺癌细胞株的生长抑制活性及与转化生长因子 - β受体 ( TGF- β R) 和 基因表达之间的关系。方法 :采用 [3 H]结合法检测 5个乳腺癌细胞株( MCF- 7、YCC- B1 0 1、YCC- B1 5 1、MDA- MB- 2 31和 SK- BR- 3) TGF-β的生长抑制反应 ,同时利用Southern、Northern和 Western blothybridization检测 TGF-β R基因的表达。结果 :3个乳腺癌细胞株 ( MCF- 7、YCC- B1 0 1和 YCC- B1 5 1 )对 TGF-β的生长抑制活性有抵抗性 ,MCF- 7细胞株几乎不表达 TGF- β R 、m RNA和 R 蛋白 ,但显示正常的 R 基因及 R 基因表达。在 YCC- B1 0 1和YCC- B1 5 1细胞株中没有检测到 TGF- β R 、R 基因表达的 m RNA和蛋白 ,但其基因结构无异常。结论 :在 MCF- 7细胞株中 ,癌细胞对 TGF- β生长抑制作用抵抗性的获得可能是 R 转录调节系统缺陷所致 ,而在 YCC- B1 0 1和 YCC- B1 5 1细胞株中 ,癌细胞对 TGF-

Objective: To examine the correlation between the growth inhibitory activity of TGF β and the genetic expression of TGF β RⅠ and RⅡ genes in human breast cancer cell lines. Methods: The growth inhibitory activity of TGF β in five breast cancer cell lines were examined by incorporation of thymidine. Southern blot, Northern blot and Western blot hybridization were performed to detect the expression of TGF β R gene. Results: Three breast cancer cell lines(MCF 7, YCC B101, YCC B151 and TGF β) were found to be resistant to growth inhibitory effect of TGF β.MCF 7 cell line ,however, expressed no detectable TGF β RⅡ mRNA and RⅡ protein, while structure of TGF β RⅡ gene and normal expression of TGF β RⅠ gene were normal. No any abnormal expression of mRNA, protein and genetic structure of TGF β RⅠ and RⅡ was found in YCC B101 and YCC B151. Conclusion: The results suggested that acquired resistance to the growth inhibitory effect of TGF β could be derived from defect of transcription regulation system of TGF β RⅡ in MCF 7 cell line, and might be in the pathway of postreceptor signal transduction in YCC B101 and YCC B151 cell lines.