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BRCA1 Protein Expression Level and CD44+ Phenotype in Breast Cancer Patients
oleh: Saadat Molanae, Mohsen Asadi-Lari, Zahra Madjd, Adel Karimi
Format: | Article |
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Diterbitkan: | Royan Institute (ACECR), Tehran 2011-01-01 |
Deskripsi
Objective: CD44+/CD24-/low breast cancer cells have tumour-initiating properties with stemcell-like features. Breast cancer gene 1 (BRCA1) is a tumour suppressor gene that playsa crucial role in DNA repair and maintenance of chromosome stability. The clinicopathologicalfeatures of breast cancer in BRCA1 mutation carriers suggest that BRCA1 mayfunction as a stem-cell regulator.Materials and Methods: In the present experimental study we examined the expressionand localization of the BRCA1 protein and investigated the prognostic value aswell as its relationship with the putative cancer stem cell (CSC) marker (CD44) in 156tumour samples from a well-characterized series of unselected breast carcinomas usingimmunohistochemistry. Statistical analysis of the data was performed using SPSSsoftware version 16 (Chicago, IL, USA).Results: In breast tumours, the loss of nuclear expression was detected in 23 cases(15%), whereas cytoplasmic expression of BRCA1 was observed in 133 breast carcinomas(85%). Altered BRCA1 expression was significantly associated with high grade and poorprognosis breast tumours (p=0.006). We further established an inverse significant correlationbetween BRCA1 expression levels and CD44+ cancer cell phenotype (p=0.02)Conclusion: Loss of BRCA1 expression is a marker of tumour aggressiveness andcorrelates with CD44+ tumour cell phenotype. Taken together, the present study supportsthe idea that the loss of BRCA1 results in persistent errors in DNA replication inbreast stem cells and provides targets for additional carcinogenic events.