Tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone suppresses a newly identified anti-tumor IGFBP-3/IGFBP-3R system in lung cancer cells
Tobacco specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone suppresses a newly identified anti-tumor IGFBP-3/IGFBP-3R system in lung cancer cells
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DOI：
10.1016/j.lungcan.2013.02.016
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发表时间：
2013-06-01
期刊：
影响因子：
5.3
通讯作者：
Oh, Youngman
中科院分区：
文献类型：
--
作者：
Harada, Aki;Jogie-Brahim, Sherryline;Oh, Youngman
IGFBP-3是一种肿瘤抑制因子，其表达在肺癌中经常受到抑制。NNK是最有效的烟草致癌物，通过DNA甲基化增强BEAS-2B正常肺上皮细胞的细胞增殖并伴随抑制IGFBP-3表达。在烟草致癌物诱导的BEAS-2 B的致瘤衍生物中检测到IGFBP-3表达降低和磷酸化Akt、磷酸化p65-NF-κ B和细胞周期蛋白D1水平升高。IGFBP-3在NNKA中的过表达抑制了NF-κ B B的活性并诱导了细胞凋亡，而内源性IGFBP-3受体（IGFBP-3特异性受体）的敲低则阻碍了这一过程。这些结果表明，NNK抑制IGFBP-3表达，从而消除IGFBP-3/IGFBP-3R系统在吸烟诱导的肺癌中的抗肿瘤作用。(C)2013爱思唯尔爱尔兰有限公司版权所有。
IGFBP-3 is a tumor suppressor whose expression is frequently suppressed in lung cancer. NNK, the most potent tobacco carcinogen, enhanced cell proliferation of BEAS-2B normal lung epithelial cells and concomitantly suppressed IGFBP-3 expression through DNA methylation. Decreased IGFBP-3 expression and elevated levels of phospho-Akt, phospho-p65-NF-kappa B, and cyclin D1 were detected in tobacco carcinogen-induced tumorigenic derivatives of BEAS-2B. Overexpression of IGFBP-3 in NNKA, one of the derivatives, suppressed NF-kappa B activity and induced apoptosis, which was hindered by knocking-down of endogenous IGFBP-3R, an IGFBP-3 specific receptor. These results suggest that NNK inhibits IGFBP-3 expression to abrogate anti-tumor actions of the IGFBP-3/IGFBP-3R system in smoking-induced lung cancer. (C) 2013 Elsevier Ireland Ltd. All rights reserved.