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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Furuta, Saori Cheng, Eric Lee, Wen-hwa Jiang, Xianzhi Gu, Bingnan Chen, Phang-lang |
| Description | Author Affiliation: Furuta S ( Department of Biological Chemistry, College of Medicine, University of California, Irvine, CA 92697, USA.); |
| Abstract | Cumulative evidence indicates that breast cancer-associated gene 1 (BRCA1) participates in DNA damage repair and cell-cycle checkpoint control, serving as a tumor susceptibility gene to maintain the global genomic stability. However, whether BRCA1 has a direct role in cell proliferation and differentiation, two key biological functions in tumorigenesis, remains unclear. Here we demonstrate BRCA1 mediates differentiation of mammary epithelial cell (MEC) for acinus formation by using the in vitro 3D culture system. Reduction of BRCA1 in MEC by RNA interference impairs the acinus formation but enhances proliferation. Such aberrations can be rescued by expression of wild-type BRCA1 as well as a mutant at the RAD50-binding domain but not at the C-terminal BRCT domain, suggesting that the C-terminal BRCT domain has a critical role in these processes. Consistently, depletion of BRCA1 up-regulates the gene expression for proliferation but down-regulates that for differentiation. Moreover, application of the medium conditioned by differentiating normal MEC can reverse the phenotypes of differentiation-defective breast cancer cells bearing reduced BRCA1 functions. Our observation implies BRCA1 is involved in secretion of certain paracrine/autocrine factors that induce MEC differentiation in response to extracellular matrix signals, providing, in part, an explanation for the etiological basis of either sporadic or familial breast cancer due to the loss or reduction of BRCA1. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 26 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-06-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | BRCA1 Protein Physiology Epithelial Cells Metabolism Gene Expression Regulation, Neoplastic Genes, BRCA1 Mammary Glands, Human Adenoviridae Genetics Breast Neoplasms Cell Culture Techniques Cell Differentiation Cell Line, Tumor Cell Proliferation Culture Media, Conditioned Pharmacology Down-Regulation Extracellular Matrix Genetic Vectors Imaging, Three-Dimensional Microscopy, Fluorescence Models, Genetic Molecular Sequence Data Mutation Phenotype Plasmids Point Mutation Protein Structure, Tertiary RNA Chemistry RNA Interference Retinoblastoma Protein Up-Regulation Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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