The breast and ovarian cancer susceptibility gene BRCA1 encodes a tumor suppressor. BRCA1 protein, which is involved in DNA damage response , has been thought to be found primarily in cell nuclei. In the present investigation , immunohistological studies of BRCA1 protein in frozen breast cancer tissue and MCF7 and HeLa cell lines revealed BRCA1 expression in both nucleoli and nucleoplasmic foci. The majority of known cancer-causing BRCA1 mutations induce protein truncation, highlighting a requirement for the BRCA1 C-terminal domain repeats in mediating BRCA1 tumor suppressor function. However, somatic mutations in BRCA1 have not been found in sporadic breast cancer tumor tissue. 5 Instead it is thought that BRCA1 participates in the tumorigenesis of sporadic breast cancer through reduction in BRCA1 mRNA and protein levels, as compared with normal tissue.
-10Functionally, BRCA1 participates in many signaling pathways involved in transcription and checkpoint control, and is recruited for the formation of DNA repair complexes, in association with proteins such as Mre11-Nbs1-Rad50, and BRCA2.11 Cell cycle studies have shown that BRCA1 protein is found in nuclear foci (dots) during S-phase, and after ␥-irradiation BRCA1 colocalizes with BRCA1-associated ring domain and Rad51-containing foci.
12Our immunohistological studies of frozen tissue sections from breast carcinomas and transmission electron microscopic studies of estrogen-stimulated MCF7 cells have shown nuclear, nucleolar, and cytoplasmic BRCA1 protein staining. 13,14 With transmission electron microscopy, we found the BRCA1 nuclear staining on the periphery of dots, around nucleoli, and also in the cytoplasm in
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