Deletion of the PER3 gene on chromosome 1p36 in recurrent ER-positive breast cancer.
J Clin Oncol
; 28(23): 3770-8, 2010 Aug 10.
Article
em En
| MEDLINE
| ID: mdl-20625127
ABSTRACT
PURPOSE:
To investigate the role of the PER3 circadian rhythm gene, located within the commonly deleted region of chromosome 1p36, in human breast cancer development. PATIENTS ANDMETHODS:
The frequency of genetic alterations at 1p36 and PER3 gene copy number status were analyzed in 180 lymph node-negative breast cancers from patients who had received treatment with chemotherapy and/or tamoxifen. The expression levels of PER3 were also analyzed using published microarray profiles from > 400 breast cancer samples. Finally, the effect of loss of Per3 on tumor susceptibility was tested using two mouse models of breast cancer.RESULTS:
Deletion of PER3 is directly related to tumor recurrence in patients with estrogen receptor (ER) - positive breast cancers treated with tamoxifen. Low expression of PER3 mRNA is associated with poor prognosis, particularly in a subset of tumors that are ER positive, and either luminal A or ERBB2-positive tumors. Mice deficient in Per3 showed increased susceptibility to breast cancer induced by carcinogen treatment or by overexpression of Erbb2.CONCLUSION:
Disruption of PER3 function may serve as an indicator of probability of tumor recurrence in patients with ER-positive tumors. Further investigations of this pathway may reveal links between deregulation of sleep homeostasis and breast tumorigenesis.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromossomos Humanos Par 1
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Neoplasias da Mama
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Proteínas Circadianas Period
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Female
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Humans
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article