Discrepancy between transcriptional products and cell surface expression of MHC class I antigens in metastatic and non-metastatic Lewis lung tumor cells.
Major histocompatibility complex class I transcriptional products and cell surface expression of their corresponding proteins were measured in tumorigenic Lewis lung carcinoma cells with either high metastatic activity (G4 cells) or with no metastatic activity (G2 cells). The transcriptional products were measured by hybridization to gene-specific oligonucleotide probes for H-2Kb and H-2Db respectively. The cell surface density of the corresponding H-2 glycoproteins was determined by FACS cell sorter analysis and by radioimmunoassay using anti-H-2Kb and anti-H-2Db specific monoclonal antibodies. The analyses revealed that the cell surface density of both Kb and Db was reduced 4-9 fold in G4 cells compared to G2 cells. However, this reduction of G4 cell surface expression of MHC class I molecules was not reflected at the mRNA level since both subclones had similar low levels of detectable Kb and Db specific mRNA. beta 2-microglobulin was analysed at the mRNA and protein level and found not to be the rate-limiting factor in the MHC class I expression of the metastatic G4 cells. Thus, the cell surface expression of H-2Kb and H-2Db by the two Lewis lung carcinoma subclones did not correlate with the amount of specific mRNA. Other regulatory mechanisms of gene expression acting at the levels between transcription and the appearance of the gene product at the cell surface must therefore account for the observed difference in the cell surface expression of MHC class I molecules of the two Lewis lung carcinoma cells. The potential importance of MHC class I expression in the metastatic capacity of the tumor cells is discussed.
Cancer Biology Laboratory, State University Hospital (Rigshospitalet), Copenhagen, Denmark.
H R
HR
Juul-Madsen
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L
Olsson
D000818:Animals; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D002460:Cell Line; D002462:Cell Membrane / Q000276:immunology; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005805:Genes, MHC Class I; D015395:Histocompatibility Antigens Class I / Q000032:analysis / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D015345:Oligonucleotide Probes; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger; D011863:Radioimmunoassay; D011951:Receptors, Complement / Q000032:analysis*; D017463:Receptors, Complement 3b; D015183:Restriction Mapping; D014158:Transcription, Genetic; D001613:beta 2-Microglobulin / Q000235:genetics
D000911:Antibodies, Monoclonal; D004273:DNA, Neoplasm; D015395:Histocompatibility Antigens Class I; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; D001613:beta 2-Microglobulin; D011061:Poly A; D012313:RNA