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Titolo:
TAUTOMYCIN - AN INHIBITOR OF PROTEIN PHOSPHATASE-1 AND PHOSPHSTASE-2ABUT NOT A TUMOR PROMOTER ON MOUSE SKIN AND IN RAT GLANDULAR STOMACH
Autore:
SUGANUMA M; OKABE S; SUEOKA E; NISHIWAKI R; KOMORI A; UDA N; ISONO K; FUJIKI H;
Indirizzi:
SAITAMA CANC CTR,RES INST INA SAITAMA 362 JAPAN SAITAMA CANC CTR,RES INST INA SAITAMA 362 JAPAN RIKEN,INST PHYS & CHEM RES WAKO SAITAMA 35101 JAPAN
Titolo Testata:
Journal of cancer research and clinical oncology
fascicolo: 9-10, volume: 121, anno: 1995,
pagine: 621 - 627
SICI:
0171-5216(1995)121:9-10<621:T-AIOP>2.0.ZU;2-T
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN MYELOID-LEUKEMIA; NECROSIS-FACTOR-ALPHA; OKADAIC ACID; GENE-EXPRESSION; POTENT; KERATINOCYTES; TOXIN; CELLS;
Keywords:
TAUTOMYCIN; OKADAIC ACID; PROTEIN PHOSPHATASES 1 AND 2A; TUMOR PROMOTION; TUMOR NECROSIS FACTOR ALPHA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
33
Recensione:
Indirizzi per estratti:
Citazione:
M. Suganuma et al., "TAUTOMYCIN - AN INHIBITOR OF PROTEIN PHOSPHATASE-1 AND PHOSPHSTASE-2ABUT NOT A TUMOR PROMOTER ON MOUSE SKIN AND IN RAT GLANDULAR STOMACH", Journal of cancer research and clinical oncology, 121(9-10), 1995, pp. 621-627

Abstract

Tautomycin isolated from Streptomyces spiroverticillatus is an inhibitor of protein phosphatases 1 and 2A. Tautomycin induced hyperphosphorylation of cytokeratin peptides in human keratinocytes (PHK 16-I cells) 30 times less strongly than did okadaic acid. Repeated applications of tautomycin (30 mu g, 40 nmol/application) did not induce tumor promotion in a two-stage carcinogenesis experiment on mouse skin initiatedwith 7,12-dimethylbenz[a]anthracene, whereas okadaic acid (1 mu g, 1.2 nmol/application) application) as a control induced tumor promotion strongly. As for mucosa of rat glandular stomach, tautomycin induced ornithine decarboxylase 4 h after intubation into the stomach. The tumor-promoting activity of tautomycin was next studied in the glandular stomach initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Administration of tautomycin in the diet (1 mg rat(-1) day(-1)), from week 9 to week 52 of the experiment, inhibited rather than enhanced tumordevelopment in the glandular stomach initiated with MNNG. The percentages of tumor-bearing rats of the groups treated with MNNG plus tautomycin, MNNG alone, and tautomycin alone were 20.0%, 40.6%, and 0% respectively in week 52. The reason for the absence of tumor-promoting activity of tautomycin was studied in relation to tumor necrosis factor alpha (TNF alpha), an endogenous tumor promoter. We found that tautomycin neither enhanced TNF alpha mRNA expression in mouse skin nor inducedTNF alpha release in a human stomach cancer cell line (KATO III cells), whereas okadaic acid did both. These results indicate that not all inhibitors of protein phosphatases are tumor promoters, and suggest that tumor promotion of the okadaic acid class of compounds is mediated by TNF alpha.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 15/07/20 alle ore 04:10:28