Direct IFNluence of interferon-gamma on proliferation and cell-surface antigen expression of non-small cell lung cancer cells.
In order to clarify the anti-tumor activity of IFN-gamma, we investigated the direct IFNluence of IFN-gamma on both the growth and cell-surface antigen expression of tumor cells. In the present study, four human lung cancer cell lines were used; two squamous cell lines (QG-56, QG-95) and two adenocarcinoma cell lines (PC-9, PC-12). In all four tumor cell lines, mutations were detected in exon 7 of the p53 gene by a PCR-FSSCP analysis. The proliferation of QG-56 or QG-95 was inhibited by IFN-gamma in a dose-dependent manner with about 70% inhibition at 1000 JRU/ml while that of PC-9 was slightly inhibited with maximally 25% inhibition at 1000 JRU/ml. The growth of PC-12 was not inhibited at all. In QG-56, QG-95 and PC-9, the fraction of cells in G1 phase increased while the fractions of cells in both S and G2/M phases decreased after exposure to IFN-gamma (200 JRU/ml) for 72 h. The growth inhibition by long-term exposure to IFN-gamma was irreversible in QG-56. After culture in the presence of IFN-gamma (200 JRU/ml) for 14-16 days, tumor cells were examined for expression of various antigens, including HLA-class I, HLA-class II, and CEA. In all cell lines but PC-12, 100% of cells expressed HLA-class I after incubation with IFN-gamma. Both HLA-class II and CEA were also induced in those cell lines. The proportion of HLA-class II-positive cells or that of CEA-positive cells varied among the cell lines. Of the three antigens, the degree of HLA-class II expression paralleled that of growth inhibition by IFN-gamma treatment. These results suggested that in various function of IFN-gamma against tumor cells, the anti-proliferative effect might be closely linked with the induction of HLA-class II probably through a similar posttranscriptional process, independent of the function of p53 gene.
Yano
T
T
Department of Thoracic Surgery, National Kyushu Medical Center, Fukuoka, Japan.
Sugio
K
K
Yamazaki
K
K
Kase
S
S
Yamaguchi
M
M
Ondo
K
K
Sugimachi
K
K
D000954:Antigens, Surface / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology*; D002455:Cell Division / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D006649:Histocompatibility Antigens / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology*; D012323:RNA Processing, Post-Transcriptional; D014407:Tumor Cells, Cultured
D000954:Antigens, Surface; D006649:Histocompatibility Antigens; D007371:Interferon-gamma