Analysis of p16 and p21(Cip1) expression in tumorigenic human bronchial epithelial cells induced by asbestos.
Although asbestos is carcinogenic to humans, the mechanism(s) by which it induces cancer is unknown. Using tumor cell lines generated previously by asbestos treatment of immortalized human bronchial epithelial (BEP2D) cells, we examined alterations in p16 and p21(Cip1) genes together with their protein levels. Results were compared with untreated BEP2D cells, normal human bronchial epithelial cells (NHBE), as well as non-tumorigenic fusion cell lines generated by fusing tumor cells with BEP2D cells. No deletion in the p16 gene was found in any of the tumor cell lines examined. Although p16 protein was expressed at a similar level in tumor and BEP2D cells, there was a fourfold decrease in its expression among NHBE cells. In contrast, both the protein and mRNA expression levels of p21(Cip1) were decreased by about threefold in tumor cell lines when compared with either BEP2D or NHBE cells, which had a similar expression level. Expression of p21(Cip1) mRNA was restored to the control level in all the fusion cell lines examined. The results suggested that down regulation of p21(Cip1) expression is linked to the tumorigenic conversion of BEP2D cells by asbestos.
Piao
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Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA. cp16@columbia.edu
Zhao
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Hei
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TK
D001194:Asbestos / Q000009:adverse effects*; D017632:Asbestos, Serpentine / Q000633:toxicity; D001980:Bronchi / Q000473:pathology*; D002273:Carcinogens / Q000009:adverse effects*; D002461:Cell Line, Transformed / Q000378:metabolism / Q000637:transplantation; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019942:Genes, p16; D006801:Humans; D006822:Hybrid Cells / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000209:etiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000637:transplantation
D017632:Asbestos, Serpentine; C493956:CDKN1A protein, human; D002273:Carcinogens; D016895:Culture Media, Serum-Free; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D001194:Asbestos