Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression.
Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression.
复制标题
DOI：
10.1016/j.bbrc.2011.08.047
复制
发表时间：
2011-09-16
影响因子：
3.1
通讯作者：
Hosoi, Hajime
中科院分区：
文献类型：
--
作者：
Katsumi, Yoshiki;Iehara, Tomoko;Miyachi, Mitsuru;Yagyu, Shigeki;Tsubai-Shimizu, Satoko;Kikuchi, Ken;Tamura, Shinichi;Kuwahara, Yasumichi;Tsuchiya, Kunihiko;Kuroda, Hiroshi;Sugimoto, Tohru;Houghton, Peter J.;Hosoi, Hajime
恶性横纹肌样瘤(MRT)是一种少见且高度侵袭性的儿童肿瘤。MRT的特征是整合酶相互作用蛋白1(INI1)失活。细胞周期蛋白依赖性激酶4(CDK4)作用于INI1下游，是MRT细胞增殖所必需的。在这里，我们研究了CDK4的有效抑制剂PD 0332991(PD)对五种人MRT细胞系(MP-MRT-AN，KP-MRT-RY，G401，KP-MRT-NS，KP-MRT-YM)的作用。流式细胞仪和BrdU掺入实验显示，除KP-MRT-YM细胞外，Pd对Kp-MRT-ym细胞的增殖抑制均为50%(IC50值为0.01~0.6µM)，并可诱导细胞周期停滞于G1期。Mrt细胞对PD的敏感性与p16表达呈负相关(r=0.951)。KP-MRT-YM细胞高表达p16，并能抵抗PD的生长抑制作用。针对p16的小干扰RNA显著增加了KP-MRT-YM细胞对PD的敏感性(p<；0.05)。这些结果表明，MRT中p16的表达可以用来预测其对PD的敏感性。对于肿瘤表达低水平p16的MRT患者，PD可能是一个有吸引力的药物。
Malignant rhabdoid tumor (MRT) is a rare and highly aggressive neoplasm of young children. MRT is characterized by inactivation of integrase interactor 1 (INI1). Cyclin-dependent kinase 4 (CDK4), which acts downstream of INI1, is required for the proliferation of MRT cells. Here we investigated the effects of PD 0332991 (PD), a potent inhibitor of CDK4, against five human MRT cell lines (MP-MRT-AN, KP-MRT-RY, G401, KP-MRT-NS, KP-MRT-YM). In all of the cell lines except KP-MRT-YM, PD inhibited cell proliferation > 50 %, (IC50 values 0.01 to 0.6 µM) by WST-8 assay, and induced G1-phase cell cycle arrest, as shown by flow cytometry and BrdU incorporation assay. The sensitivity of the MRT cell lines to PD was inversely correlated with p16 expression (r = 0.951). KP-MRT-YM cells overexpress p16 and were resistant to the growth inhibitory effect of PD. Small interfering RNA against p16 significantly increased the sensitivity of KP-MRT-YM cells to PD (p < 0.05). These results suggest that p16 expression in MRT could be used to predict its sensitivity to PD. PD may be an attractive agent for patients with MRT whose tumors express low levels of p16.
登录
查看更多内容
影响因子：
11.2
作者：
Kuwahara Y;Charboneau A;Knudsen ES;Weissman BE
通讯作者：
Weissman BE
影响因子：
11.2
作者：
Baughn, Linda B.;Di Liberto, Maurizio;Chen-Kiang, Selina
通讯作者：
Chen-Kiang, Selina
影响因子：
8
作者：
Dean, J. L.;Thangavel, C.;Knudsen, E. S.
通讯作者：
Knudsen, E. S.
影响因子：
5.3
作者：
Zhang, ZK;Davies, KP;Kalpana, GV
通讯作者：
Kalpana, GV
影响因子：
11.2
作者：
Michaud K;Solomon DA;Oermann E;Kim JS;Zhong WZ;Prados MD;Ozawa T;James CD;Waldman T
通讯作者：
Waldman T