사람 방광암 세포주에서 IFN-γ에 의한 ICAM-1 및 HLA-DR의 유도 발현

Abstract

Four human bladder cancer cell lines, RT4(gI, well differentiated, superficial TCC), T24(GII, epidermoid, superficial TCC), J82(GIII, anaplastic, invasive TCC0, TCCSUP(GIV, distant metastatic TCC) and one normla fetus bladder cell line, FHs7381B1, were analyzed for their ability to expres the ICAM-I and ILA-DR molecules at the trancriptional level as well as on their cell surfaces before and after treatment with 200U/ml of IFN-ν. All cell lines except RT4, even though the intensity of ICAM-1 expression was enormously stronger in normal fetus blader cell line comparing to T24, J82 and TCCSUP, displayed consitutive expression of ICAM-1 before and after IFN-ν treament. RT4 cells did not express ICAM-1 regardless of IFN-νtreamtnet. Before IFN-νtreamtnet, HLA-DR was not constitutively expressed in all cell lines. After 200U/ml of IFN-ν treament, RT4 derived from patient with benign clinical course and j82 derived from patient without distant metastasis displayed elevated levels of HLADR expression which reached to the almost maximum level after IFN-νtreament for 48hr. The exprsion rate and the degree of HLA-DR expression in these cell lines increased in a time dependent manner but HLA-DR expresion was not induced in the T24 and TCCSUP cell lines even at a higher concentration (1000U/mll) of IFN-ν. The molecular mechanism underlying such a differential expression was investigated and the HLA-DR gene regulation was studied at the transcriptional level. In RT4 and J82 cell lines, treatment with IFN-νled to the steady-state mRNA augmentation of the HLA-DR gene. The HLA-DR A mRNA augmentotion was similar in both cell lines, whereas HLA-DR B mRNA augmentation was higher in RT4 than in J82. These results established that the human bladder cancer cell studied here showed a diffential susceptibility to IFN-νon the modulation of HLA-DR molecules, and this modulation is transcriptioally regulated. By analysing above findings along with clinical characteristics of patients from whom the cell lines were stablished, it might be also suggested that the expression of ICAM-1 seems to be associated with cell differentiation and the iducibility of HLA-DR expression by IFN-νseems to be associated with clinical course and/or metastatic potential of bladder cancer.