Catechol estrogen metabolites and conjugates in mammary tumors and hyperplastic tissue from estrogen receptor-alpha knock-out (ERKO)/Wnt-1 mice: implications for initiation of mammary tumors.
Carcinogenesis
; 22(9): 1573-6, 2001 Sep.
Article
em En
| MEDLINE
| ID: mdl-11532882
ABSTRACT
A novel model of breast cancer was established by crossing mice carrying the Wnt-1 transgene (100% of adult females develop spontaneous mammary tumors) with the ERKO mouse line, in which mammary tumors develop despite a lack of functional estrogen receptor-alpha. To begin investigating whether metabolite-mediated genotoxicity of estrogens may play an important role in the initiation of mammary tumors, the pattern of estrogen metabolites and conjugates was examined in ERKO/Wnt-1 mice. Extracts of hyperplastic mammary tissue and mammary tumors were analyzed by HPLC with identification and quantification of compounds by multichannel electrochemical detection. Picomole amounts of the 4-catechol estrogens (CE) were detected, but their methoxy conjugates, as well as the 2-CE and their methoxy conjugates, were not. 4-CE conjugates with glutathione or its hydrolytic products (cysteine and N-acetylcysteine) were detected in picomole amounts in both tumors and hyperplastic mammary tissue, demonstrating the formation of CE-3,4-quinones. These preliminary findings show that the estrogen metabolite profile in the mammary tissue is unbalanced, in that the normally minor 4-CE metabolites were detected in the mammary tissue and not the normally predominant 2-CE. These results are consistent with the hypothesis that the mammary tumor development is primarily initiated by metabolism of estrogens to 4-CE and, then, to CE-3,4-quinones, which may react with DNA to induce oncogenic mutations.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
/
Estrogênios de Catecol
/
Proteínas de Peixe-Zebra
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Glândulas Mamárias Animais
/
Neoplasias Mamárias Experimentais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Carcinogenesis
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos