title: Downregulation of ALDH1A1 expression in non-small cell lung carcinomas--its clinicopathologic and biological significance.
abstract: ALDH1A1 metabolizes a variety of endogenous and exogenous aldehyde, and also oxidizes retinol to synthesize retinoic acid and modulate cell differentiation. Moreover, ALDH1A1 is also suggested to participate in the maintenance of cancer stem cells. To investigate the potential role of ALDH1A1 in carcinogenesis of the lung, the present study examined two hundred and sixty eight cases of non-small cell lung carcinoma (NSCLC) for its immunohistochemical expression and analyzed associations between ALDH1A1 levels and a series of clinicopathologic parameters. Also, the biological significance of the aberrant expression of ALDH1A1 was investigated in vitro. ALDH1A1 expression was markedly reduced in 39.9% (107/268) of NSCLCs. The incidence of this reduction was significantly higher in adenocarcinomas (ADC: 41.6%, 85/207) and large cell carcinomas (61.1%, 11/18) than squamous cell carcinomas (25.5%, 11/43). Among ADCs, the downregulation tended to be more remarkable in high grade, poorly differentiated tumors, and tumors with stronger proliferating activity. It also occurred with a significantly higher incidence in smokers than non-smokers. Forced expression of ALDH1A1 in NSCLC cell lines, which had lost ALDH1A1 expression, markedly attenuated their growth. Taken together, loss of ALDH1A1 expression is suggested to promote carcinogenesis especially in the smoking-related ADCs.
authors.affiliation: Department of Pathology, Yokohama City University Graduate School of Medicine 3-9, Fukuura, Kanazawa-ku, 236-0004, Yokohama, Japan. kojixok@yokohama-cu.ac.jp
authors.forename: Koji
authors.initials: K
authors.lastname: Okudela
authors.forename: Tetsukan
authors.initials: T
authors.lastname: Woo
authors.forename: Hideaki
authors.initials: H
authors.lastname: Mitsui
authors.forename: Takeshisa
authors.initials: T
authors.lastname: Suzuki
authors.forename: Michihiko
authors.initials: M
authors.lastname: Tajiri
authors.forename: Yuji
authors.initials: Y
authors.lastname: Sakuma
authors.forename: Yohei
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tateishi
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Umeda
authors.forename: Munetaka
authors.initials: M
authors.lastname: Masuda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Ohashi
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000032:analysis / Q000096:biosynthesis*; D000080924:Aldehyde Dehydrogenase 1 Family; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000473:pathology; D015536:Down-Regulation; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000473:pathology; D009367:Neoplasm Staging; D050697:Retinal Dehydrogenase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects
chemical_list: D014408:Biomarkers, Tumor; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase