Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14
Inhibitor of growth 4 is involved in melanomagenesis and induces growth suppression and apoptosis in melanoma cell line M14
复制标题
生长抑制剂 4 参与黑色素瘤生成并诱导黑色素瘤细胞系 M14 生长抑制和凋亡
DOI：
10.1097/cmr.0b013e32831bc42f
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发表时间：
2009-02-01
影响因子：
2.2
通讯作者：
Sun, Jianfang
中科院分区：
文献类型：
--
作者：
Cai, Limin;Li, Xiaomei;Sun, Jianfang
本研究的目的如下。生长抑制剂（Inhibitor of growth，ING）4是ING家族的新成员。它被认为通过参与基因转录、细胞凋亡、细胞周期调控和肿瘤血管生成而在多种恶性肿瘤中发挥抑制作用。ING 4在黑色素瘤发生中的作用尚不清楚。本研究旨在探讨ING 4对黑色素瘤的抑制作用及其机制。方法：构建重组质粒pcDNA3.1-ING 4，转染人黑色素瘤细胞系M14。采用MTT法、克隆形成实验、TUNEL法等方法分析ING 4对M14细胞增殖和凋亡的影响及其机制。Western blot检测转染后M14细胞中细胞周期和凋亡调控因子的表达。免疫组化法检测黑色素瘤组织中ING 4的表达。ING 4在皮肤黑色素瘤组织中的表达显著降低。ING 4过表达可诱导M14细胞生长抑制和凋亡增强，并诱导p27、Bax和Cyt-c表达上调，cyclinD 1、SKP 2、Bcl-2和caspase-3表达下调。结论：ING 4作为一种新型的肿瘤抑制因子，通过激活肿瘤诱导的凋亡途径和阻碍细胞周期进程，在抑制黑色素瘤M14的生长和促进细胞凋亡中具有潜在的作用。ING 4的异常表达可能参与了黑色素瘤的发生。
The objective of this study is as follows. Inhibitor of growth (ING) 4 is a novel member of the ING family. It has been thought to play an inhibitory role in several malignancies through its involvment in gene transcription, apoptosis, cell cycle control, and tumor angiogenesis. The involvement of ING4 in melanomagenesis remains unknown. The purpose of this study was to investigate the inhibitory effects of ING4 on melanoma and its mechanisms. The method used was to construct recombinant plasmid pcDNA3.1-ING4 and transfect it into the human melanoma cell line M14. The effects and mechanisms of ING4 on proliferation and apoptosis of M14 cells were analyzed in vitro according to MTT assay, colony formation assay, and TUNEL assay. The detection of the expression of cell cycle or apoptosis regulators in transfected M14 cells was carried out by western blot analysis. Moreover, the level of ING4 in melanoma tissues was examined by immunohistochemistry. The expression of ING4 was markedly reduced in cutaneous melanoma tissues. Overexpression of ING4 could induce growth suppression and apoptosis enhancement in M14 cells, and also induce the upregulation of p27, Bax and Cyt-c, and the downregulation of cyclinD1, SKP2, Bcl-2, and caspase-3. In conclusion, ING4, as a novel tumor suppressor, has a potential role in growth suppression and apoptosis enhancement of melanoma M14 through the activation of the mitochondrial-induced apoptotic pathway and the hindrance of cell cycle progression. The deregulation of ING4 might be involved in melanomagenesis.