title: Cyclooxygenase-2 expression during immortalization and breast cancer progression.
abstract: 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.
authors.affiliation: Division of Cancer Biology, Department of Medicine, Evanston Northwestern Healthcare Research Institute and Feinberg School of Medicine, Evanston, IL, USA.
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Zhao
authors.forename: Monica
authors.initials: M
authors.lastname: Goswami
authors.forename: Nidhi
authors.initials: N
authors.lastname: Pokhriyal
authors.forename: Hui
authors.initials: H
authors.lastname: Ma
authors.forename: Hongyan
authors.initials: H
authors.lastname: Du
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Victor
authors.forename: Kornelia
authors.initials: K
authors.lastname: Polyak
authors.forename: Charles D
authors.initials: CD
authors.lastname: Sturgis
authors.forename: Hamid
authors.initials: H
authors.lastname: Band
authors.forename: Vimla
authors.initials: V
authors.lastname: Band
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000473:pathology; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D005348:Fibrocystic Breast Disease / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D010641:Phenotype
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human