AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating CDKI-cyclin D1 and caspase-3 activity
AKAP12 induces apoptotic cell death in human fibrosarcoma cells by regulating CDKI-cyclin D1 and caspase-3 activity
复制标题
DOI：
10.1016/j.canlet.2007.02.017
复制
发表时间：
2007-08-28
期刊：
影响因子：
9.7
通讯作者：
Kim, Kyu-Won
中科院分区：
文献类型：
--
作者：
Yoon, Dae-Kwan;Jeong, Chul-Ho;Kim, Kyu-Won
AKAP 12（A-Kinase anchoring protein 12）是一种蛋白激酶C底物，是一种潜在的肿瘤抑制因子。AKAP 12被几种癌基因下调，并在包括前列腺癌、卵巢癌和乳腺癌在内的各种癌症中受到强烈抑制。AKAP 12通过锚定关键信号蛋白如PKA、PKC和细胞周期蛋白作为有丝分裂的调节剂。在这项研究中，AKAP 12被发现通过在HT 1080细胞中通过caspase-3诱导凋亡来抑制肿瘤细胞活力。AKAP 12诱导的细胞凋亡与Bcl-2的表达减少和Bax的表达增加有关。此外，AKAP 12转染子强烈诱导Cip 1/p21和Kip 1/p27的表达，但导致参与G（1）进展的cyclin D1的减少。因此，这些结果表明，AKAP 12可能通过诱导细胞凋亡并调节细胞周期进程中的多个分子而在肿瘤生长抑制中发挥重要作用。(c)2007年由Elsevier爱尔兰有限公司出版。
AKAP12 (A-Kinase anchoring protein 12) is a protein kinase C substrate and a potential tumor suppressor. AKAP12 is down-regulated by several oncogenes and strongly suppressed in various cancers including prostate, ovarian and breast cancers. AKAP12 acts as a regulator of mitogenesis by anchoring key signal proteins such as PKA, PKC, and cyclins. In this study, AKAP12 was found to suppress tumor cell viability by inducing apoptosis via caspase-3 in HT1080 cells. This AKAP12-induced apoptosis was associated with a decreased expression of Bcl-2 and increased expression of Bax. Moreover, AKAP12-transfectant strongly induced the expression of Cip1/p21 and Kip1/p27, but resulted in a decrease in cyclin D1 involved in G(1) progression. Accordingly, these results suggest that AKAP12 may play an important role in tumor growth suppression by inducing apoptosis with the regulation of multiple molecules in the cell cycle progression. (c) 2007 Published by Elsevier Ireland Ltd.