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Cell, Tumor, and Stem Cell Biology |
Divisions of 1 Cancer Biology and 2 Molecular Oncology, Department of Medicine, 3 Department of Pathology, and 4 Center for Outcome Research and Education, Evanston Northwestern Healthcare Research Institute and Feinberg School of Medicine; 5 Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois; and 6 Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts
Requests for reprints: Vimla Band, Department of Genetics, Cell Biology & Anatomy, University of Nebraska Medical Center, DRC 6th Floor, 985805 Nebraska Medical Center, Omaha, NE 68198-5805. Phone: 402-559-8565; Fax: 402-559-7328; E-mail: vband{at}unmc.edu.
Identification of molecular aberrations in premalignant human mammary epithelial cells (hMEC), the precursors for breast cancers, is a central goal in breast cancer biology. Recent studies implicated expression of cyclooxygenase 2 (COX-2) as a marker to identify precursor cells for breast cancer. In this study, we analyzed COX-2 expression in preselection and postselection hMEC cells and observed similar COX-2 levels in both cells. Interestingly, immortalization of postselection cells using various methods leads to a dramatic decrease in COX-2 expression. Similar to immortal cells, the majority of breast cancer cell lines expressed low levels of COX-2 protein. Finally, analyses of COX-2 expression in a series of specimens from reduction mammoplasty, adenosis, ductal carcinoma in situ, and infiltrating ductal carcinoma showed down-regulation of COX-2 expression during tumor progression. Importantly, down-regulation of COX-2 using small interfering RNA in cells showed no effect on cell proliferation, anchorage-independent growth, migration, or invasion. These results show that (a) COX-2 overexpression does not seem to predict a breast cancer precursor cell and does not provide advantage for the cell to be transformed; (b) inhibition of COX-2 does not affect hMEC growth and oncogenic behavior in the conditions analyzed; and (c) COX-2 expression is decreased in breast cancer cell lines and cancer specimens as compared with normal mammary epithelial cells. [Cancer Res 2008;68(2):467–75]
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Correction: COX-2 Expression Decreases in Breast Cancer Progression Cancer Res., March 1, 2008; 68(5): 1609 - 1609. [Full Text] [PDF] |
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