BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays

Mahmoud, Abeer M.; Macias, Virgilia; Al-Alem, Umaima; Deaton, Ryan; Kadjaksy-Balla, Andre; Gann, Peter H.; Rauscher, Garth H.

doi:10.1371/journal.pone.0184385

Cited by 17 publications

(18 citation statements)

References 38 publications

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“…In this study we found that BRCA1 protein was expressed in 10% of breast cancer, this study is supported by study of Dokyung et al [13]. who reported that BRCA protein was expressed in 24.7% of breast cancers, In the present study we also found the expression of BRCA1protein in breast cancer is higher than in normal breast lesion, this finding is inconsistent with the study of [14] who reported that a high uniform expression of BRCA1 was observed in normal breast tissue while absent or reduced expression was found only in malignant tissues.…”

Section: Discussioncontrasting

confidence: 78%

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Osman¹,

Eltom²,

Abdallah³

et al. 2020

JCT

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Background: Knowledge of HER2/Neu and BRCA1 Genes might be helpful for development of strategies for decreasing the burden of risk of breast cancer. Therefore, the aim of this study to detect the role of HER2/Neu and BRCA1 Genes expression in diagnosis of breast cancer in Sudanese women. Methodology: A total of 100 tissue samples obtained from patients with breast cancer in addition to 50 tissue samples obtained from patients with benign breast lesions, were detected the expression of HER2/Neu and BRCA1 Genes by Polymerase Chain Reaction (PCR). Results: The prevalence of HER2/Neu and BRCA1 Genes, among cases was 6%, and 10% respectively. Conclusion: HER2/Neu and BRCA1 Genes have a considerable contribution to etiology of breast cancer in Sudan that requires further consideration.

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Section: Discussioncontrasting

confidence: 78%

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Osman¹,

Eltom²,

Abdallah³

et al. 2020

JCT

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“…We detected BRCA1 in the nuclei and cytosol of vCTs. Cytosolic BRCA1 location has been associated with highly proliferating breast cancer tumors [46]. Its presence in the cytosol of vCTs reflects the high proliferative potential, as can be expected from the trophoblast stem cell population.…”

Section: Discussionmentioning

confidence: 99%

Maternal Obesity Alters Placental Cell Cycle Regulators in the First Trimester of Human Pregnancy: New Insights for BRCA1

Hoch

Bachbauer

Pöchlauer

et al. 2020

IJMS

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In the first trimester of pregnancy, placental development involves a wide range of cellular processes. These include trophoblast proliferation, fusion, and differentiation, which are dependent on tight cell cycle control. The intrauterine environment affects placental development, which also includes the trophoblast cell cycle. In this work, we focus on maternal obesity to assess whether an altered intrauterine milieu modulates expression and protein levels of placental cell cycle regulators in early human pregnancy. For this purpose, we use first trimester placental tissue from lean and obese women (gestational week 5+0–11+6, n = 58). Using a PCR panel, a cell cycle protein array, and STRING database analysis, we identify a network of cell cycle regulators increased by maternal obesity in which breast cancer 1 (BRCA1) is a central player. Immunostaining localizes BRCA1 predominantly to the villous and the extravillous cytotrophoblast. Obesity-driven BRCA1 upregulation is not able to be explained by DNA methylation (EPIC array) or by short-term treatment of chorionic villous explants at 2.5% oxygen with tumor necrosis factor α (TNF-α) (50 mg/mL), leptin (100 mg/mL), interleukin 6 (IL-6) (100 mg/mL), or high glucose (25 nM). Oxygen tension rises during the first trimester, but this change in vitro has no effect on BRCA1 (2.5% and 6.5% O2). We conclude that maternal obesity affects placental cell cycle regulation and speculate this may alter placental development.

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“…In fact, 20% of sporadic breast tumors [14] did not show BRCA1 staining in either the nucleus or cytoplasm, which demonstrated a defect in protein production. In some cases, breast tumor cells showed cytoplasmic BRCA1 retention along with a loss of nuclear staining [15], which implied a defect in nuclear transportation [42,43]. These BRCA1 protein-loss tumor cells were associated with poor prognosis and might induce high BRCA1 gene expression via auto-regulation.…”

Section: Discussionmentioning

confidence: 99%

“…Loss of BRCA1 function increases ER-coactivator association in tamoxifen treated cancer cells, which leads to tamoxifen resistance [10]. In fact, decreased BRCA1 protein staining is commonly observed in sporadic breast cancers [14,15] and this phenomenon is associated with high histologic grades [16][17][18] and short disease-free survival [19]. It is certain that such association is related to an E-ER signaling pathway.…”

Section: Introductionmentioning

confidence: 99%

High BRCA1 Gene Expression Increases the Risk of Early Onset Distant Metastasis in ER+ Breast Cancers

Chang¹,

Yang²,

Lai³

et al. 2020

Preprint

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BackgroundMore than 30% of ER+ breast cancer patients developed distant metastasis after adjuvant tamoxifen therapy. It has been shown that decreased BRCA1 protein function confers anti-estrogen “resistance.” Since the functional status of BRCA1 protein auto-regulates its own gene expression, BRCA1 transcript level should possibly be used to assess its active protein levels. Thus, it is interesting to explore the potential links between BRCA1 gene expression status and the prognosis of ER+ breast tumors.MethodsEarly-staged ER+ Breast cancer microarray samples were selected from the NCBI Gene Expression Omnibus (GEO) database. The aggressiveness of these tumors was evaluated based on molecular subtypes or patients’ distant metastasis-free survival (DMFS) time found in associated GEO datasets. In survival analysis, the optimal threshold to define high and low transcript levels was assessed by the logistic-accelerated failure time mixture regression model in a pooled data set, which simultaneously envisages the lifetime risk of distant metastasis and the distribution of the DMFS time from the surgery of a patient susceptible to distant metastasis. ResultsOn the basis of molecular subtyping, the relatively aggressive Luminal B tumor cells expressed significantly more BRCA1 transcripts than the less aggressive Luminal A tumor cells. This observation was supported by DMFS time analysis. When the upper 10% of the high BRCA1 expression patients was compared with the rest of the patients, the result was quite drastic. In patients susceptible to distant metastasis, the median onset time of distant metastasis for high BRCA1 expression group (2.2 years) was about one-fifth of the BRCA1 low expression group (10.5 years).ConclusionsHigh BRCA1 transcript level does not increase the incidence of distant metastasis, but increases the risk of early onset distant metastasis in ER+ breast cancers. As new therapeutic drugs have been developed for tumors with BRCA function loss, our findings suggest that BRCA1 gene expression test not only is useful for predicting patients’ outcome but also can be used in treatment decision.

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BRCA1 protein expression and subcellular localization in primary breast cancer: Automated digital microscopy analysis of tissue microarrays

Cited by 17 publications

References 38 publications

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

The Role of HER2/Neu and BRCA1 Genes in the Diagnosis of Breast Cancer among Sudanese Women

Maternal Obesity Alters Placental Cell Cycle Regulators in the First Trimester of Human Pregnancy: New Insights for BRCA1

High BRCA1 Gene Expression Increases the Risk of Early Onset Distant Metastasis in ER+ Breast Cancers

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