Cyclooxygenase-2 expression during immortalization and breast cancer progression.
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.
Zhao
Xiangshan
X
Division of Cancer Biology, Department of Medicine, Evanston Northwestern Healthcare Research Institute and Feinberg School of Medicine, Evanston, IL, USA.
Goswami
Monica
M
Pokhriyal
Nidhi
N
Ma
Hui
H
Du
Hongyan
H
Yao
Jun
J
Victor
Thomas A
TA
Polyak
Kornelia
K
Sturgis
Charles D
CD
Band
Hamid
H
Band
Vimla
V
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
D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human