TGF-β对卵巢癌细胞生长抑制的研究

目的 :检测 14株卵巢癌细胞系中TβRⅡ、Smad4、CDC2 5A和C myc的表达情况 ,并确定这些基因的表达与TGF β去敏感的相关性。 方法 :用MTT法检测TGF β抑制卵巢癌细胞系生长的情况 ,半定量RT PCR方法检测卵巢癌细胞中TβRⅡ、Smad4、CDC2 5A和C myc的mRNA水平。结果 :14株卵巢癌细胞系中均有TβRⅡ表达 ;与正常卵巢组织相比 ,10株卵巢癌细胞系中Smad4表达下降 ,9株中CDC2 5A过度表达 ;在致瘤性细胞系中CDC 2 5AmRNA过度表达者占 88% (8/ 9) ,在非致瘤性细胞系中 ,仅占 2 0 % (1/ 5 ,P <0 .0 5 ) ;所有卵巢癌细胞系中均无C myc过度表达。结论 :卵巢癌细胞系对TGF β去敏感的可能原因是 :诱导生长抑制的转导子Smad4表达下降 ,和 (或 )CDC2 5A过度表达 ,并且这种过度表达与卵巢癌细胞系致瘤性增强相关 ,TGF β去敏感与TβRⅡ缺乏无关。

The study on the TGF-β to inhibit the ovarian cancer cell growth

Objective:To investigate the potential association between loss of sensitivity to transforming growth factor β (TGF β) and expression status of transforming growth factor receptor II (TβRII),Smad4,CDC25A and c myc in fourteen cell lines derived from ovarian cancer.Methods:Growth repression effect of TGF β was determined by MTT assay.The expression levels of these genes were examined by semi quantitative RT PCR.Normal ovarian tissues were used as controls.Tumorigenicity of ovarian cancer cell lines was examined by xenografts. Results: Expression of TβRII was detectable in all of fourteen cell lines.Expression of Smad4 was decreased in ten cell lines and nine cell lines overexpressed CDC25A,compared with normal controls.CDC25A gene was overexpressed in 88% (8/9) of tumorigenic cell lines as determined by xenografts in nude mice, and only in 20% (1/5) of non tumorigenic cell lines (P<0.05). C myc was not overexpressed in any of these cell lines. Conclusions:The loss of sensitivity to TGF β of cell lines derived from ovarian cancers may be related to (1) a decreased expression of Smad4, which mediates TGF β induced growth inhibition;and/or (2) an overexpression of CDC25A.This overexpression correlates with increased tumorigenicity.The loss of sensitivity to TGF β is not associated with a lack of TβRII.