Nature Genetics
9, 444 - 450 (1995)
doi:10.1038/ng0495-444
Decreased expression of BRCA1 accelerates growth and is often present during sporadic breast cancer progressionMarilyn E. Thompson1, Roy A. Jensen1, 2, Patrice S. Obermiller1, David L. Page2, 3
& Jeffrey T. Holt1, 2
1Departments of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
2Departments of Pathology Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
3Departments of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA Correspondence should be addressed to J.T.H. We have characterized expression of the familial breast and ovarian cancer gene, BRCA1, in cases of non−hereditary (sporadic) breast cancer and analyzed the effect of antisense inhibition of BRCA1 on the proliferative rate of mammary epithelial cells. BRCA1 mRNA levels are markedly decreased during the transition from carcinoma in situ to invasive cancer. Experimental inhibition of BRCA1 expression with antisense oligonucleotides produced accelerated growth of normal and malignant mammary cells, but had no effect on non−mammary epithelial cells. These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression.
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