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PMID: 7667256 Published · ppublish English Journal Article

Immunophenotyping of melanomas for tyrosinase: implications for vaccine development.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 18 ·1995-08-29 ·Pages 8125-9

Chen YT, Stockert E, Tsang S, Coplan KA, Old LJ

Abstract

Tyrosinase (EC 1.14.18.1), the key enzyme in melanin synthesis, has been shown to be one of the targets for cytotoxic T-cell recognition in melanoma patients. To develop serological reagents useful for immunophenotyping melanoma for tyrosinase, human tyrosinase cDNA was expressed in an Escherichia coli expression vector. The purified recombinant tyrosinase was used to generate mouse monoclonal and rabbit polyclonal antibodies. The prototype monoclonal antibody, T311, recognized a cluster of protein moieties ranging from 70 to 80 kDa in tyrosinase mRNA-positive melanoma cell lines and melanoma specimens as well as in L cells transfected with tyrosinase cDNA. Untransfected L cells and L cells transfected with tyrosinase-related protein 1, TRP-1(gp75), were nonreactive. Immunohistochemical analysis of melanomas with T311 showed tyrosinase in melanotic and amelanotic variants, and tyrosinase expression correlated with the presence of tyrosinase mRNA. Melanocytes in skin stained with T311, whereas other normal tissues tested were negative. The expression pattern of three melanosome-associated proteins--tyrosinase, TRP-1(gp75), and gp100--in melanoma was also compared. Tyrosinase and gp100 are expressed in a higher percentage of melanomas than TRP-1(gp75), and the expression of these three antigens was discordant. Tyrosinase expression within individual tumor specimen is usually homogenous, distinctly different from the commonly observed heterogeneous pattern of gp100 expression.

MeSH Terms
Amino Acid Sequence Animals Antibodies, Monoclonal/biosynthesis Base Sequence Blotting, Western Cell Line Cross Reactions DNA, Complementary Humans Immunohistochemistry Immunophenotyping Immunotherapy L Cells Melanoma/enzymology,immunology,metabolism,therapy Membrane Glycoproteins/genetics,immunology,metabolism Mice Molecular Sequence Data Monophenol Monooxygenase/genetics,immunology Neoplasm Proteins/genetics,immunology,metabolism Oxidoreductases Proteins/genetics,immunology,metabolism RNA, Messenger/genetics,metabolism Recombinant Proteins/genetics,immunology,metabolism Tumor Cells, Cultured gp100 Melanoma Antigen
Chemicals
Antibodies, Monoclonal DNA, Complementary Membrane Glycoproteins Neoplasm Proteins PMEL protein, human Pmel protein, mouse Proteins RNA, Messenger Recombinant Proteins gp100 Melanoma Antigen Oxidoreductases TYRP1 protein, human Tyrp1 protein, mouse tyrosinase-related protein-1 Monophenol Monooxygenase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chen Y T
Ludwig Institute for Cancer Research, New York Unit, Memorial Sloan-Kettering Cancer Center, NY 10105, USA.
Stockert E
Tsang S
Coplan K A
Old L J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.18.8125
Published
1995-08-29
Pages
8125-9
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41108
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.18.8125 PMC Full Text View journal details
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