Induction of ICAM-1, HLA-DR Molecules by IFN-Gamma and Oncogene Expression in Human Bladder Cancer Cell Lines

Abstract

It is well known that the expression level of the ICAM-1 and MHC is frequently altered in accordance with tumor progression, and the expression of oncogenes is significantly related to tumorigenesis, tumor progression, and/or metastatic potential. In this study, to investigate the relationship between the alteration in ICAM-1 and MHC expression with the tumor grade and/or cell differentiation, we examined the expression of ICAM-1 and HLA-DR before and after treatment with IFN-gamma in 4 human bladder cancer cell lines. We also analyzed the expression of c-Ha-ras and c-myc. Using flow cytometry, highly constitutive expression of ICAM-1 was detected in all cell lines tested except RT4 (grade I, well-differentiated, superficial). IFN-gamma was found to somewhat induce the expression of ICAM-1 in all cell lines except RT4. The constitutive expression of HLA-DR was not detected in any of the cell lines tested by flow cytometry and Northern blot. HLA-DR expression was induced by IFN-gamma in RT4 and J82 (grade III, anaplastic, invasive). Codon 12 point mutation of c-Ha-ras (GGC-->GTC; Gly-->Val) was detected in T24 (grade III, epidermoid, superficial) through single-strand conformation polymorphism, and sequencing analysis. Another point mutation at codon 27 was detected in TCCSUP (grade IV, distant metastatic), but this mutation was found to be silent (CAT-->CAC; His). Expression of c-myc was detected in J82 and TCCSUP by Northern blot. These findings, along with the clinical and pathological characteristics of the patients from whom the cell lines were established, might suggest that the expression of ICAM-1 seems to be associated with cell differentiation, and the inducibility of HLA-DR by IFN-gamma seems to be associated with the degree of malignancy. Expression of c-myc seems to be associated with invasiveness. However, a significant correlation between c-Ha-ras activation and tumor grade could not be observed.