title: Alteration of transcriptional profile in human bronchial epithelial cells induced by cigarette smoke condensate.
abstract: Despite the significance of cigarette smoke for carcinogenesis, the molecular mechanisms that lead to increased susceptibility of human cancers are not well-understood. In our present study, the oncogenic transforming effects of cigarette smoke condensate (CSC) were examined using papillomavirus-immortalized human bronchial epithelial cells (BEP2D). Growth kinetics, saturation density, resistance to serum-induced terminal differentiation, anchorage-independent growth and tumorigenicity in nude mice were used to investigate the various stages of transformation in BEP2D cells. Illumina microarray platforms were used to explore the CSC-induced alteration of global mRNA expression profiles of the earlier period and the advanced stage of CSC-treated BEP2D cells. We showed here that a series of sequential steps arose among CSC-treated immortalized human bronchial epithelial cells, including altered growth kinetics, resistance to serum-induced terminal differentiation, and anchorage-independence growth. In the earlier period of CSC treatment, 265 genes were down-regulated and 63 genes were up-regulated, respectively, and in the advanced stage of CSC treatment, 313 genes were down-regulated and 145 genes were up-regulated, respectively. Notably, among those genes, the expression of some of imprinted genes such as IGF2, NDN, H19 and MEG3 were all silenced or down-regulated in CSC-treated cells. These genes reactivated after 5 microM 5-aza-2-deoxycytidine (5-aza-dC) treatment. These results demonstrated that long-term treatment of human bronchial epithelial cells with CSC may adversely affect their genetic and epigenetic integrity and lead to further transformation.
authors: Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Haidian District, Beijing 100850, PR China.
authors: Ying-Chun
authors: YC
authors: Hu
authors: Zhi-Hua
authors: ZH
authors: Yang
authors: Ke-Jun
authors: KJ
authors: Zhong
authors: Li-Jing
authors: LJ
authors: Niu
authors: Xiu-Jie
authors: XJ
authors: Pan
authors: De-Chang
authors: DC
authors: Wu
authors: Xian-Jun
authors: XJ
authors: Sun
authors: Ping-Kun
authors: PK
authors: Zhou
authors: Mao-Xiang
authors: MX
authors: Zhu
authors: Yan-Ying
authors: YY
authors: Huo
mesh_terms: D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015152:Blotting, Northern; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000187:drug effects; D000077209:Decitabine; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014026:Nicotiana / Q000737:chemistry / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D000077209:Decitabine; D001374:Azacitidine