GANP protein encoded on human chromosome 21/mouse chromosome 10 is associated with resistance to mammary tumor development.
Cancer Sci
; 107(4): 469-77, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26749495
ABSTRACT
Human chromosome 21 is known to be associated with the high risk of hematological malignancy but with resistance to breast cancer in the study of Down syndrome. In human cancers, we previously observed the significant alterations of the protein expression encoded by the ganp/MCM3AP gene on human chromosome 21q22.3. Here, we investigated GANP protein alterations in human breast cancer samples (416 cases) at various stages by immunohistochemical analysis. This cohort study clearly showed that expression of GANP is significantly decreased in human breast cancer cases with poor prognosis as an independent risk factor (relapse-free survival, hazard ratio = 2.37, 95% confidence interval, 1.27-4.42, P = 0.007 [univariate analysis]; hazard ratio = 2.70, 95% confidence interval, 1.42-5.13, P = 0.002 [multivariate analysis]). To investigate whether the altered GANP expression is associated with mammary tumorigenesis, we created mutant mice that were conditionally deficient in the ganp/MCM3AP gene using wap-cre recombinase transgenic mice. Mammary gland tumors occurred at a very high incidence in female mammary gland-specific GANP-deficient mice after severe impairment of mammary gland development during pregnancy. Moreover, tumor development also occurred in female post parous GANP-heterodeficient mice. GANP has a significant role in the suppression of DNA damage caused by estrogen in human breast cancer cell lines. These results indicated that the GANP protein is associated with breast cancer resistance.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Acetiltransferases
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Neoplasias da Mama
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Neoplasias Mamárias Animais
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Peptídeos e Proteínas de Sinalização Intracelular
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Recidiva Local de Neoplasia
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Middle aged
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Pregnancy
Idioma:
En
Revista:
Cancer Sci
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Japão