Abstract |
The lack of HLA class I antigen expression by the melanoma cell line SK-MEL-33 is caused by a unique lesion in beta 2-microglobulin (beta 2-mu). Sequencing of beta 2-mu mRNA detected a guanosine deletion at position 323 in codon 76 that causes a frameshift with a subsequent introduction of a stop codon at a position 54 base upstream of the normal position of the stop codon in the message. The loss of 18 amino acids and the change of 6 amino acids, including a cysteine at position 80 in the carboxy terminus of beta 2-mu, are likely to cause marked changes in the structure of the polypeptide. The latter may account for the inability of beta 2-mu to associate with HLA class I heavy chains and for its lack of reactivity with the anti-beta 2-mu mAb tested. HLA class I antigen expression on SK-MEL-33 cells was reconstituted after transfection with a wild-type B2m gene, therefore indicating that the abnormality of endogenous B2m gene is the only mechanism underlying lack of HLA class I antigen expression by SK-MEL-33 cells. The guanosine deletion in B2m gene was detected also in the melanoma tissue from which SK-MEL-33 cells had originated. Therefore, the molecular lesion identified in the SK-MEL-33 melanoma cell line is not caused by a mutation acquired during growth in vitro but is likely to reflect a somatic mutation during tumor progression.
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Authors | Z Wang, Y Cao, A P Albino, R A Zeff, A Houghton, S Ferrone |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 91
Issue 2
Pg. 684-92
(Feb 1993)
ISSN: 0021-9738 [Print] United States |
PMID | 8432869
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Histocompatibility Antigens Class I
- RNA, Messenger
- beta 2-Microglobulin
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Topics |
- Aged
- Base Sequence
- Frameshift Mutation
- Gene Deletion
- Histocompatibility Antigens Class I
(analysis)
- Humans
- Male
- Melanoma
(genetics, immunology)
- Molecular Sequence Data
- RNA, Messenger
(genetics)
- Transfection
- Tumor Cells, Cultured
- beta 2-Microglobulin
(genetics)
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