Subcellular localization of BRCA1 protein in sporadic breast carcinoma with or without allelic loss of BRCA1 gene.

Bernard‐Gallon, Dominique; Latour, Monique Peffault De; Rio, Pascale; Penault‐Llorca, Frédérique; Favy, D; Hızel, Candan; Chassagne, J; Bignon, Yves‐Jean

doi:10.3892/ijo.14.4.653

Cited by 6 publications

(6 citation statements)

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“…This agrees with data from a previous report 29 in which only cytoplasmic staining was seen using polyclonal antibodies D-20, I-20, K-18, and C-20 on paraYn wax embedded samples. Our results diVer from those of Jarvis, 26 who found diVerences in nuclear staining of tumour cells with the D-20 antibody, the cytoplasm being positive in all sporadic breast cancers tested.…”

Section: Discussionsupporting

confidence: 92%

“…33 Concentrations of the BRCA1 protein are also decreased in mammary tumours compared with matched normal breast tissue, 36 implying multiple mechanisms of BRCA1 expression downregulation in these tumours. Other data suggest that the reduced expression of the BRCA1 protein might play an important role in mammary carcinogenesis in sporadic cancer, and that mechanisms other than mutation, 19 21 in particular LOH, 29 might be involved in the reduced expression of the BRCA1 protein. Taken together, our data support the notion that the N-terminal specific MS110 antibody is not useful in prescreening BRCA1 mutations because it has a lower rate of detection in breast tumours from patients carrying a BRCA1 gene mutation than in tumours, both familial (65%) or sporadic (50%), from patients without BRCA1 germline mutations.…”

Section: Discussionmentioning

confidence: 99%

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The usefulness of antibodies to the BRCA1 protein in detecting the mutated BRCA1 gene. An immunohistochemical study

Pérez‐Vallés

Martorell-Cebollada²,

Nogueira-Vázquez³

et al. 2001

Journal of Clinical Pathology

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Aim-To assess the value of immunohistochemistry in discriminating between BRCA1 associated and non-BRCA1 associated breast tumours. Methods-Four Conclusions-Commerciallyavailable BRCA1 antibodies lack the specificity required to identify the BRCA1 protein and thus are not useful for establishing diVerences between familial and sporadic breast tumours, or between BRCA1 associated and non-BRCA1 associated breast tumours. (J Clin Pathol 2001;54:476-480)

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

The usefulness of antibodies to the BRCA1 protein in detecting the mutated BRCA1 gene. An immunohistochemical study

Pérez‐Vallés

Martorell-Cebollada²,

Nogueira-Vázquez³

et al. 2001

Journal of Clinical Pathology

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“…However, only the 11% (19 of 178) of breast cancer specimens displayed aberrant methylation of BRCA1, indicating that hypermethylation alone could not explain the 82% of aggressive breast cancer specimens that were reported to have weak or no BRCA1 protein expression (51). Similarly, loss of heterozygosity at the BRCA1 locus proved insufficient as an explanation for the low levels of BRCA1 expression in breast carcinomas, since studies showed that loss of heterozygosity correlated with reduced BRCA1 expression in only a few cases (7,37,45,49).…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have demonstrated that BRCA1 protein levels are decreased in a subset of sporadic breast carcinomas compared to normal breast tissues (7,37,48,45,51,52). The majority of high-grade ductal carcinomas lack BRCA1 protein or have low levels (51), supporting the idea of a potentially central role for BRCA1 in the pathogenesis of a significant percentage of noninherited breast cancers.…”

Section: Discussionmentioning

confidence: 99%

Negative Regulation of BRCA1 Gene Expression by HMGA1 Proteins Accounts for the Reduced BRCA1 Protein Levels in Sporadic Breast Carcinoma

Baldassarre

Battista

Belletti

et al. 2003

Molecular and Cellular Biology

116

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A drastic reduction in BRCA1 gene expression is a characteristic feature of aggressive sporadic breast carcinoma. However, the mechanisms underlying BRCA1 downregulation in breast cancer are not well understood. Here we report that both in vitro and in vivo HMGA1b protein binds to and inhibits the activity of both human and mouse BRCA1 promoters. Consistently, murine embryonic stem (ES) cells with the Hmga1 gene deleted display higher Brca1 mRNA and protein levels than do wild-type ES cells. Stable transfection of MCF-7 cells with the HMGA1b cDNA results in a decrease of BRCA1 gene expression and in a lack of BRCA1 induction after estrogen treatment. Finally, we found an inverse correlation between HMGA1 and BRCA1 mRNA and protein expression in human mammary carcinoma cell lines and tissues. These data indicate that HMGA1 proteins are involved in transcriptional regulation of the BRCA1 gene, and their overexpression may have a role in BRCA1 downregulation observed in aggressive mammary carcinomas.BRCA1 was isolated as the gene responsible for increased susceptibility to familial breast and ovarian cancer (31). Germ line mutations of BRCA1 have been detected in approximately 90% of familial breast and ovarian cancers and in approximately 50% of familial breast cancers alone. Full-length BRCA1 is a nuclear protein of 220 kDa and 1,863 amino acids. The BRCA1 gene is highly expressed in rapidly proliferating mammary epithelial cells during pregnancy and is downregulated during lactation (30, 39). BRCA1 has pleiotropic biological functions, possibly playing a role in transcriptional regulation, chromatin remodeling, DNA damage repair, cell cycle regulation, and checkpoint control (reviewed in reference 43).Although BRCA1 mutations play a critical role in familial breast carcinomas, sporadic breast carcinomas rarely show mutations in the BRCA1 gene (21). However, reduced expression of BRCA1 has been frequently observed in sporadic breast carcinomas, and reduced expression of BRCA1 has shown a positive correlation with increased invasiveness of human breast carcinomas (49, 51).Many studies have examined the downregulation of BRCA1 expression in advanced sporadic cancer, but the mechanisms for this remain poorly understood. Alterations of methylation patterns are rarely detected in the vicinity of the major transcription initiation site of the BRCA1 gene (9,11,16,29,36), and loss of heterozygosity is not related with BRCA1 mRNA and protein expression level (26,40,49). Therefore, different mechanisms may account for the inactivation of BRCA1 function in sporadic breast cancer.HMGA1 is a structural gene that encodes a nonhistone chromatin protein. Two isoforms, HMGA1a and HMGA1b, are produced through an alternative splicing mechanism. Both isoforms are able to bind DNA in AT-rich regions and interact with various transcription factors to enhance or inhibit gene transcription by acting as architectural proteins (reviewed in reference 35). HMGA1 protein is abundant during embryogenesis (12, 53) but is absent or present only...

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“…The implication of specific genes, such as BRCA1 and BRCA2 tumor suppressor genes, has been shown in mammary carcinogenesis. In sporadic breast cancers, specific modifications of BRCA1 and BRCA2 mRNA expression have been reported too (Bernard-Gallon et al, 1999;Bieche et al, 1999). Epigenetic modifications such as promoter hypermethylation of the oncosuppressor genes BRCA1 and BRCA2 can play a role in the oncogenesis of cancer (Esteller et al, 2000).…”

mentioning

confidence: 99%

BRCA2 Promoter Hypermethylation in Sporadic Breast Cancer

Bosviel

Durif

Guo

et al. 2012

OMICS: A Journal of Integrative Biology

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Subcellular localization of BRCA1 protein in sporadic breast carcinoma with or without allelic loss of BRCA1 gene.

Cited by 6 publications

References 0 publications

The usefulness of antibodies to the BRCA1 protein in detecting the mutated BRCA1 gene. An immunohistochemical study

The usefulness of antibodies to the BRCA1 protein in detecting the mutated BRCA1 gene. An immunohistochemical study

Negative Regulation of BRCA1 Gene Expression by HMGA1 Proteins Accounts for the Reduced BRCA1 Protein Levels in Sporadic Breast Carcinoma

BRCA2 Promoter Hypermethylation in Sporadic Breast Cancer

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