Malignant Transformation and Abnormal Expression of Eukaryotic Initiation Factor in Bronchial Epithelial Cells Induced by Cadmium Chloride

Key words: 
• Cell transformation /
• Tumorigenicity /
• Eukaryotic initiation factor 3 /
• Cadmium chloride /
• Human bronchial epithelial cells

Abstract: To analyze the relationship between malignant transformation and abnormal expression of eukaryotic initiation factor 3 (eIF3 p36) in human bronchial epithelial (16HBE) cells induced by cadmium chloride (CdCl<,2>). Methods 16HBE cellswere treated several dmes with different concentrations of CdCl<,2>. Tumorigenic potential of transformed cells was identified by assays for anchorage-independent growth in soft agar and for tumorigenicity in nude mice after the 35th passage. Total RNA was isolated from 16HBE cells induced by CdCl<,2>, including non-transformed, Cd-transformed, and Cd-tumorigenic cell lines. Special primers for eIF3 p36 were designed and the expression of eIF3 mRNA in different cell lines was detected with fluorescent quantitative-polymerase chain reaction technique (FQ-PCR). Results The 35th passage of 16HBE cells transformed by CdCl<,2> exhibited overlapping growth. Compared with the non-transformed cells, colonies of transformed cell lines in soft agar showed statistically significant increases and dose-dependent effects (P<0.01). All Cd-induced transformed cell lines formed tumors in nude mice within 2 weeks of inoculation, but none of the mice injected with non-transformed cells showed tumors even after 3 weeks. All tumors were pathologically identified as poorly differentiated squamous cell carcinoma. The eIF3 p36 genes in different stages of 16HBE cells transformed by CdCl<,2> were elevated as compared with the non-transformed control (P<0.01), and the eIF3 expression increased with the degree of cell malignancy. Conclusion CdCl<,2> is capable of inducing morphological transformation in 16HBE cells and transformed cells are potentially tumorigenic. Over-expression of eIF3 p36 is positively correlated with malignant transformation of 16HBE cells induced by CdCl<,2> and may be one of the molecular mechanisms potentially responsible for carcinogenesis due to Cd.