Disease relevance of BRAP

• CONCLUSIONS: BRCA1, as well as TP53, can undergo LOH prior to stromal invasion in BRCA1-associated ovarian cancer [1].
• Patients with BRCA1-associated breast cancer had twice as many progesterone-receptor-negative tumours (p<0.005) and development of contralateral breast cancer was four to five times as frequent as in the sporadic group (p<0.001) [2].
• BRCA1-associated breast cancers are more frequently ductal invasive, high-grade carcinomas with an important lymphocytic infiltration [3].
• Low frequency of lymph-node metastasis in BRCA1-associated breast cancer [4].
• The recent observation that studies of BRCA1-associated tumors contain a high proportion of medullary carcinomas and ductal carcinomas with medullary features has re-introduced pathologists to an old diagnostic problem [5].

High impact information on BRAP

• The mRNA polyadenylation factor CstF interacts with the BRCA1-associated protein BARD1, and this interaction represses the nuclear mRNA polyadenylation machinery in vitro [6].
• We report the identities of the members of a group of proteins that associate with BRCA1 to form a large complex that we have named BASC (BRCA1-associated genome surveillance complex) [7].
• Histology of BRCA1-associated ovarian tumours [8].
• Modification of BRCA1-associated breast cancer risk by the polymorphic androgen-receptor CAG repeat [9].
• Brap2 functions as a cytoplasmic retention protein for p21 during monocyte differentiation [10].

Chemical compound and disease context of BRAP

• These results suggest that pathways involving androgen signaling may affect the risk of BRCA1-associated breast cancer [9].
• Expression of steroid hormone receptors in BRCA1-associated ovarian carcinomas [11].

Biological context of BRAP

• Monocytic differentiation of the promyelomonocytic cell lines U937 and HL60 is associated with the upregulation of Brap2 expression concomitantly with the upregulation and cytoplasmic relocalization of p21 [10].
• BRAP2 also shares significant homology with a hypothetical protein from yeast Saccharomyces cerevisiae, especially in the zinc finger region [12].
• The characteristic phenotype of BRCA1-associated tumors may prove a useful additional tool in selecting individuals with breast cancer who should be offered BRCA1 mutation testing, although further studies are required [13].
• We identified IFI16 as a BRCA1-associated protein involved in p53-mediated apoptosis [14].
• While BRCA1 plays an active role in DNA repair, this function alone may not be sufficient to explain why BRCA1-associated tumors predominantly occur in estrogen-responsive tissues [15].

Anatomical context of BRAP

• Here we characterize one of the other clones identified, BRAP2, which is a novel gene and expressed as a 2-kilobase mRNA in human mammary epithelial cells and some but not all tissues of mice [12].
• Our aim was to test whether the proliferation rate of BRCA1-associated breast cancers was affected by the site of the germ line mutation in the BRCA1 gene [16].
• We conclude that despite the tremendous shuffling of chromosomes during the course of mammalian evolution, the pattern of genomic imbalances is conserved between BRCA1-associated mammary gland tumors in mice and humans [17].

Associations of BRAP with chemical compounds

• Antibodies prepared against the C-terminal region of BRAP2 fused to glutathione S-transferase specifically recognize a cellular protein with a molecular size of 68 kDa, consistent with the size of the in vitro translated protein [12].
• RESULTS: We found that only breast cancers from young (<50 years) BRCA1+ patients represent features documented as being typical of BRCA1-associated cancers, such as high tumour grade, negativity for oestrogen and progesterone receptors, and overexpression of p53 [18].

Physical interactions of BRAP

• Cellular BRAP2 is mainly cytoplasmic and binds to the NLS motifs of BRCA1 with similar specificity to that of importin alpha in both two-hybrid assays in yeast and glutathione S-transferase pull-down assays in vitro [12].

Regulatory relationships of BRAP

• The E3 ubiquitin ligase IMP (impedes mitogenic signal propagation) was isolated as a novel Ras effector that negatively regulates ERK1/2 activation [19].

Other interactions of BRAP

• Disruption of the BRCA1-associated protein BARD1 had effects similar to those of mutation of BRCA1 [20].
• Specific emphasis is placed on genetic alterations and the prevalence of TP53 (p53) gene alterations in the distinct biological ovarian tumors (benign, borderline, and malignant) and histological subtypes (serous, mucinous, endometrioid, clear cell), as well as in BRCA1-associated hereditary ovarian cancer [21].
• Fas ligand expression in BRCA1-associated hereditary breast carcinoma clearly differs from that in sporadic breast carcinoma [22].

Analytical, diagnostic and therapeutic context of BRAP

• Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients [23].
• BACKGROUND: Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes [23].
• The high rate of BRCA1 carriers who received chemotherapy for their BC should question the positive impact of this treatment, as suggested by preclinical studies showing increased chemosensitivity of BRCA1-associated tumours [24].
• AIM:To assess the value of immunohistochemistry in discriminating between BRCA1 associated and non-BRCA1 associated breast tumours [25].
• BRCA1-associated HBCs showed a tendency (P = 0.06) toward an increase in solid-tubular type tumors and a significant increase in histologic grade 3 tumors (P < 0.01) and lymphatic invasion positive tumors (P < 0.05) compared with the control group [26].

References