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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• 作者：Aki Harada ; Sherryline Jogie-Brahim ; Youngman Oh ; ^{yoh@mcvh-vcu.edu}
• 关键词：IGFBP-3 ; Tobacco ; NNK ; Lung cancer ; DNA methylation ; Apoptosis
• 刊名：Lung Cancer
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：80
• 期：3
• 页码：270-277
• 全文大小：1299 K

文摘

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-¦ÊB, 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-¦ÊB 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.