Rapid induction of p21WAF1 but delayed down-regulation of Cdc25A in the TGF-beta-induced cell cycle arrest of gastric carcinoma cells.
Rapid induction of p21WAF1 but delayed down-regulation of Cdc25A in the TGF-beta-induced cell cycle arrest of gastric carcinoma cells.
复制标题
DOI：
10.1038/sj.bjc.6690478
复制
发表时间：
1999-06
影响因子：
8.8
通讯作者：
Kim, SJ
中科院分区：
文献类型：
--
作者：
Kang, SH;Bang, YJ;Jong, HS;Seo, JY;Kim, NK;Kim, SJ
转化生长因子-β（TGF-β）是一种多功能多肽，可抑制大多数上皮细胞的细胞增殖。cdk 4和几种细胞周期蛋白依赖性激酶（cdk）抑制剂（p15 INK 4 B、p21 WAF 1/Cip 1和p27 Kip 1）已经涉及TGF-β诱导的细胞周期停滞。最近，Cdc 25 A（一种cdk激活剂）的下调被认为是TGF-β抑制生长的潜在机制。然而，TGF-β的多种细胞介质的存在提出了一个问题，即它们的参与是否可能以冗余的方式或协调地发生在某种细胞类型中。利用两种TGF-β敏感的胃癌细胞系（SNU-16和SNU-620），我们通过比较几种cdk抑制剂以及cdk 4和Cdc 25 A对TGF-β诱导的细胞周期阻滞的时间表达模式来阐明它们在TGF-β诱导的细胞周期阻滞中的作用。在所检测的cdk抑制剂中，p21 mRNA被TGF-β诱导最快（小于1小时）且显著。相反，p15 mRNA在SNU-620细胞中的诱导比p21慢，并且在p15纯合缺失的SNU-16细胞中不表达。Western blotting结果证实了p21的快速增加，而在两种细胞系中观察到相反的p27表达模式。Cdc 25 A mRNA的下调发生，但比p15或p21更延迟。在G1期阻滞建立之前，Cdc 25 A和cdk 4蛋白水平的变化是微不足道的。与抗cdk 4抗体的免疫共沉淀显示诱导的p21与cdk 4缔合，并且其激酶活性被TGF-β降低，这与两种细胞系在TGF-β处理后的G1停滞在动力学上密切相关。这些结果表明，在某些人上皮细胞中，p21可能在TGF-β诱导的细胞周期阻滞中发挥早期作用，并且其与其他cdk抑制剂的合作取决于细胞类型而不同。Cdc 25 A和cdk 4的延迟下调可能有助于细胞适应静止状态的两种胃癌细胞系研究。© 1999癌症研究运动
Transforming growth factor-β (TGF-β) is a multifunctional polypeptide that inhibits cellular proliferation in most epithelial cells. cdk4 and several cyclin-dependent kinase (cdk) inhibitors (p15INK4B, p21WAF1/Cip1 and p27Kip1) have been implicated in the TGF-β-induced cell cycle arrest. More recently, down-regulation of Cdc25A, a cdk activator, was additionally suggested as a mechanism underlying growth inhibition by TGF-β. The existence of diverse cellular mediators of TGF-β, however, raises the question of whether their involvement might occur in a redundant manner or coordinately in a certain cell type. Using two TGF-β-sensitive gastric carcinoma cell lines (SNU-16 and -620), we addressed the contributory roles of several cdk inhibitors, and of cdk4 and Cdc25A, in TGF-β-induced cell cycle arrest by comparing their temporal expression pattern in response to TGF-β. Among the cdk inhibitors examined, p21 mRNA was most rapidly (in less than 1 h) and prominently induced by TGF-β. In contrast, p15 mRNA was more slowly induced than p21 in SNU-620 cells, and not expressed in SNU-16 cells harbouring homozygous deletion of p15. Western blotting results confirmed the rapid increase of p21, while opposite patterns of p27 expression were observed in the two cell lines. The down-regulation of Cdc25A mRNA occurred, but was more delayed than that of p15 or p21. Until G1 arrest was established, changes in the protein levels of both Cdc25A and cdk4 were marginal. Co-immunoprecipitation with anti-cdk4 antibody showed that induced p21 associates with cdk4 and that its kinase activity is reduced by TGF-β, which kinetically correlates closely with G1 arrest following TGF-β treatment of both cell lines. These results suggest that in certain human epithelial cells, p21 may play an early role in TGF-β-induced cell cycle arrest, and its cooperation with other cdk inhibitors is different depending on cell type. Delayed down-regulation of Cdc25A and cdk4 may contribute to cell adaptation to the quiescent state in the two gastric carcinoma cell lines studied. © 1999 Cancer Research Campaign
登录
查看更多内容
影响因子：
13
作者：
Markowitz, Sanford D.;Roberts, Anita B.
通讯作者：
Roberts, Anita B.
影响因子：
10.5
作者：
POLYAK, K;KATO, JY;KOFF, A
通讯作者：
KOFF, A
影响因子：
64.8
作者：
WRANA, JL;ATTISANO, L;MASSAGUE, J
通讯作者：
MASSAGUE, J
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
DOI：
10.1073/pnas.91.19.8772
发表时间：
1994-09-13
影响因子：
11.1
作者：
PARK, KC;KIM, SJ;SPORN, MB
通讯作者：
SPORN, MB