Insensitivity to growth inhibition by TGF-β1 correlates with a lack of inhibition of the CDK2 activity in prostate carcinoma cells
Insensitivity to growth inhibition by TGF-β1 correlates with a lack of inhibition of the CDK2 activity in prostate carcinoma cells
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DOI：
10.1038/sj.onc.1202069
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发表时间：
1998-09-24
期刊：
影响因子：
8
通讯作者：
Chen, YQ
中科院分区：
文献类型：
--
作者：
Cipriano, SC;Chen, YQ
tgf - β是一种有效的上皮细胞生长抑制剂。然而，许多转化的细胞已经失去了对这种生长抑制作用的敏感性。在此，我们研究了tgf - β 1对正常人前列腺细胞和癌细胞的影响。我们的研究结果表明，正常细胞对生长抑制敏感，而无论tgf - β 1浓度（20至80 pM）或暴露时间（1-5天）如何，肿瘤细胞都没有或只有最低限度的抑制。在正常和肿瘤细胞中，Western blotting检测到p21（WAF/Cip1/Sdi1）和p15(INK4B)，但未检测到p27(KIP1)， tgf - β 1治疗增加了正常和前列腺肿瘤细胞中p21（WAF1/Cip1/Sdi1）与Cdk2/cyclin E复合物的相关性。然而，p15（INK4B）和p27（Kip1）与Cdk/cyclin复合物的关联没有增加，在正常细胞中，p21（WAF1/Cip1/Sdi1）的关联增加。与此同时，Cdk2/cyclin E复合物导致Cdk2活性抑制。相比之下，尽管肿瘤细胞中p21（WAF1/Cip1/Sdi1）与th、Cdk2/cyclin E复合物的相关性增加，但Cdk2活性并未受到抑制，这些结果表明，缺乏对Cdk2活性的抑制与前列腺肿瘤细胞对tgf - β 1不敏感有关。
TGF-beta is a potent growth inhibitor of epithelial cells. However, many transformed cells have lost their sensitivity to this growth inhibitory effect. The molecular mechanism of such insensitivity is not get understood, Here, we have studied the TGF-beta 1 effect on normal human prostate and carcinoma cells. Our results showed that normal cells were sensitive to growth inhibition, whereas tumor cells were not or only minimally inhibited regardless of the concentration of TGF-beta 1 (20 to 80 pM) or time of exposure (1-5 days). p21(WAF/Cip1/Sdi1) and p15(INK4B) but not p27(KIP1) were detectable by Western blotting in normal and tumor cells, TGF-beta 1 treatment increased the association of p21(WAF1/Cip1/Sdi1) with the Cdk2/cyclin E complex in both normal and prostate tumor cells. However, there was no increase in the association of p15(INK4B) nor p27(Kip1) with the Cdk/cyclin complexes, In normal cells, the increase in the association of p21(WAF1/Cip1/Sdi1). With th, Cdk2/cyclin E complex resulted in inhibition of the Cdk2 activity. In contrast, although there was an increase in the association of p21(WAF1/Cip1/Sdi1) With th, Cdk2/cyclin E complex in tumor cells, there was no inhibition of the Cdk2 activity, These results indicate that a lack of inhibition of the Cdk2 activity correlates with insensitivity to TGF-beta 1 in prostate tumor cells.