C-myc Down-regulates Class I HLA Expression in Human Melanomas

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 1988 Apr 1

PMID 3402430

Citations 75

Authors

R Versteeg

I A Noordermeer

D J Ruiter

P I Schrier

Affiliations

Soon will be listed here.

Abstract

Expression of class I HLA antigen has been shown to be reduced in a number of human tumours. Here we show that in a panel of 11 melanoma cell lines with variable class I HLA expression an inverse correlation exists between the mRNA levels of c-myc and class I HLA. This suggests that high expression of the c-myc oncogene might inhibit the class I HLA expression. To test this hypothesis a melanoma cell line with a low c-myc and high class I HLA mRNA expression was transfected with a c-myc expression vector. All clones expressing the transfected c-myc gene show reduced class I HLA mRNA and beta 2-microglobulin mRNA expression. Reduced class I HLA mRNA levels result in a lowered class I protein expression on the cell surface. Treatment with gamma-interferon fully restores the class I HLA and beta 2-microglobulin expression in these cells. This effect is preceded by a transient decrease of the c-myc mRNA level. These results show that the class I HLA expression is modulated by the level of c-myc expression, thus opening up the possibility that high expression of this oncogene influences the interaction of melanoma cells with the immune system.

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References

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Land H, Parada L, Weinberg R . Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983; 304(5927):596-602. DOI: 10.1038/304596a0. View

Zinkernagel R, Doherty P . MHC-restricted cytotoxic T cells: studies on the biological role of polymorphic major transplantation antigens determining T-cell restriction-specificity, function, and responsiveness. Adv Immunol. 1979; 27:51-177. DOI: 10.1016/s0065-2776(08)60262-x. View

Aubert C, Rouge F, Galindo J . Tumorigenicity of human malignant melanocytes in nude mice in relation to their differentiation in vitro. J Natl Cancer Inst. 1980; 64(5):1029-40. View

Van Der Eb A, Graham F . Assay of transforming activity of tumor virus DNA. Methods Enzymol. 1980; 65(1):826-39. DOI: 10.1016/s0076-6879(80)65077-0. View

Auffray C, Rougeon F . Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980; 107(2):303-14. DOI: 10.1111/j.1432-1033.1980.tb06030.x. View

Sood A, Pereira D, Weissman S . Isolation and partial nucleotide sequence of a cDNA clone for human histocompatibility antigen HLA-B by use of an oligodeoxynucleotide primer. Proc Natl Acad Sci U S A. 1981; 78(1):616-20. PMC: 319105. DOI: 10.1073/pnas.78.1.616. View

Basham T, Bourgeade M, Creasey A, Merigan T . Interferon increases HLA synthesis in melanoma cells: interferon-resistant and -sensitive cell lines. Proc Natl Acad Sci U S A. 1982; 79(10):3265-9. PMC: 346396. DOI: 10.1073/pnas.79.10.3265. View

Bernards R, Houweling A, Schrier P, Bos J, Van Der Eb A . Characterization of cells transformed by Ad5/Ad12 hybrid early region I plasmids. Virology. 1982; 120(2):422-32. DOI: 10.1016/0042-6822(82)90042-3. View

10.

Rebai N, Malissen B . Structural and genetic analyses of HLA class I molecules using monoclonal xenoantibodies. Tissue Antigens. 1983; 22(2):107-17. DOI: 10.1111/j.1399-0039.1983.tb01176.x. View

11.

Feinberg A, Vogelstein B . A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983; 132(1):6-13. DOI: 10.1016/0003-2697(83)90418-9. View

12.

Schrier P, Bernards R, Vaessen R, Houweling A, Van Der Eb A . Expression of class I major histocompatibility antigens switched off by highly oncogenic adenovirus 12 in transformed rat cells. Nature. 1983; 305(5937):771-5. DOI: 10.1038/305771a0. View

13.

Kelly K, Cochran B, Stiles C, Leder P . Cell-specific regulation of the c-myc gene by lymphocyte mitogens and platelet-derived growth factor. Cell. 1983; 35(3 Pt 2):603-10. DOI: 10.1016/0092-8674(83)90092-2. View

14.

De Vries J, Spits H . Cloned human cytotoxic T lymphocyte (CTL) lines reactive with autologous melanoma cells. I. In vitro generation, isolation, and analysis to phenotype and specificity. J Immunol. 1984; 132(1):510-9. View

15.

Lee W, Murphree A, Benedict W . Expression and amplification of the N-myc gene in primary retinoblastoma. Nature. 1984; 309(5967):458-60. DOI: 10.1038/309458a0. View

16.

Knuth A, Danowski B, Oettgen H, Old L . T-cell-mediated cytotoxicity against autologous malignant melanoma: analysis with interleukin 2-dependent T-cell cultures. Proc Natl Acad Sci U S A. 1984; 81(11):3511-5. PMC: 345538. DOI: 10.1073/pnas.81.11.3511. View

17.

Ruiter D, Bergman W, Welvaart K, Scheffer E, van Vloten W, Russo C . Immunohistochemical analysis of malignant melanomas and nevocellular nevi with monoclonal antibodies to distinct monomorphic determinants of HLA antigens. Cancer Res. 1984; 44(9):3930-5. View

18.

Armelin H, Armelin M, Kelly K, Stewart T, Leder P, Cochran B . Functional role for c-myc in mitogenic response to platelet-derived growth factor. Nature. 1984; 310(5979):655-60. DOI: 10.1038/310655a0. View

19.

Hui K, Grosveld F, Festenstein H . Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature. 1984; 311(5988):750-2. DOI: 10.1038/311750a0. View

20.

Tanaka K, Isselbacher K, Khoury G, Jay G . Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science. 1985; 228(4695):26-30. DOI: 10.1126/science.3975631. View