title: 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.
abstract: 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-κB, 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-κB 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.
authors.affiliation: Department of Pathology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298, USA.
authors.forename: Aki
authors.initials: A
authors.lastname: Harada
authors.forename: Sherryline
authors.initials: S
authors.lastname: Jogie-Brahim
authors.forename: Youngman
authors.initials: Y
authors.lastname: Oh
mesh_terms: D002273:Carcinogens / Q000494:pharmacology / Q000633:toxicity; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009602:Nitrosamines / Q000494:pharmacology / Q000633:toxicity*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects; D014026:Nicotiana
chemical_list: D002273:Carcinogens; C552964:IGFBP-3R protein, human; D018972:Insulin-Like Growth Factor Binding Protein 3; D009602:Nitrosamines; D011956:Receptors, Cell Surface; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone