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Titolo:
UP-REGULATION OF SPECIFIC TYROSINASE MESSENGER-RNAS IN MOUSE MELANOMAS WITH THE C(2J) GENE SUBSTITUTED FOR THE WILD-TYPE TYROSINASE ALLELE - UTILIZATION IN DESIGN OF SYNGENEIC IMMUNOTHERAPY MODELS
Autore:
LEFUR N; SILVERS WK; KELSALL SR; MINTZ B;
Indirizzi:
FOX CHASE CANC CTR,INST CANC RES,7701 BURHOLME AVE PHILADELPHIA PA 19111 FOX CHASE CANC CTR,INST CANC RES PHILADELPHIA PA 19111
Titolo Testata:
Proceedings of the National Academy of Sciences of the United Statesof America
fascicolo: 14, volume: 94, anno: 1997,
pagine: 7561 - 7565
SICI:
0027-8424(1997)94:14<7561:UOSTMI>2.0.ZU;2-6
Fonte:
ISI
Lingua:
ENG
Soggetto:
TUMOR-INFILTRATING LYMPHOCYTES; CYTOLYTIC T-LYMPHOCYTES; MALIGNANT SKIN MELANOMA; HLA-A2 MELANOMAS; TRANSGENIC MICE; ANTIGEN; IDENTIFICATION; TRANSCRIPTS; PROGRESSION; GP100;
Keywords:
ALTERNATIVE SPLICING; MELANOCYTIC GENES; SKIN GRAFTS; MELANOMA PROGRESSION; TRANSGENIC MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
32
Recensione:
Indirizzi per estratti:
Citazione:
N. Lefur et al., "UP-REGULATION OF SPECIFIC TYROSINASE MESSENGER-RNAS IN MOUSE MELANOMAS WITH THE C(2J) GENE SUBSTITUTED FOR THE WILD-TYPE TYROSINASE ALLELE - UTILIZATION IN DESIGN OF SYNGENEIC IMMUNOTHERAPY MODELS", Proceedings of the National Academy of Sciences of the United Statesof America, 94(14), 1997, pp. 7561-7565

Abstract

The expression of cell-specialization genes is likely to be changing in tumor cells as their differentiation declines. Functional changes in these genes might yield unusual peptide epitopes with anti-tumor potential and could occur without modification in the DNA sequence of thegene. Melanomas undergo a characteristic decline in melanization thatmay reflect altered contributions of key melanocytic genes such as tyrosinase. Quantitative reverse transcriptase-PCR of the wild-type (C) tyrosinase gene in transgenic (C57BL/6 strain) mouse melanomas has revealed a shift toward alternative splicing of the pre-mRNA that generated increased levels of the Delta 1b and Delta 1d mRNA splice variants. The spontaneous c(2j) albino mutation of tyrosinase (in the C57BL/6 strain) changes the pre-mRNA splicing pattern. In c(2j)/c(2j) melanomas, alternative splicing was again increased. However, while some mRNAs (notably Delta 1b) present in C/C were obligatorily absent, others (Delta 3 and Delta 1d) were elevated. In c(2j)/c(2j) melanomas, the percentage of total tyrosinase transcripts attributable to Delta 3 reached approximately 2-fold the incidence in c(2j)/c(2j) or C/C skin melanocytes. The percentage attributable to Delta 1d rose to approximately 2-fold the incidence in c(2j)/c(2j) skin, and to 10-fold that in C/C skin. These differences provide a basis for unique mouse models in which the melanoma arises in skin grafted from a C/C or c(2j)/c(2j) transgenic donor to a transgenic host of the same or opposite tyrosinase genotype. Immunotherapy designs then could be based on augmenting those antigenic peptides that are novel or overrepresented in a tumor relative to the syngeneic host.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 19:50:56