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 i nduces cancer is unknown. Using tumor cell lines generated previously by as bestos treatment of immortalized human bronchial epithelial (BEP2D) cells, we examined alterations in p16 and p21(Cip1) genes together with their prot ein levels. Results were compared with untreated BEP2D cells, normal human bronchial epithelial cells (NHBE), as well as nontumorigenic fusion cell li nes generated by fusing tumor cells with BEP2D cells. No deletion in the p1 6 gene was found in any of the tumor cell lines examined. Although p16 prot ein 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 th reefold in tumor cell lines when compared with either BEP2D or NHBE cells, which had a similar expression level. Expression of p21(Cip1) mRNA was rest ored to the control level in all the fusion cell lines examined. The result s suggested that down regulation of p21(Cip1) expression is linked to the t umorigenic conversion of BEP2D cells by asbestos.