Surgical specimens from 44 patients with breast cancer who had undergone lumpectomy or mastectomy were analyzed by immunoblot analysis and immunohistochemical analysis to determine the expression profile of the constitutively expressed form of cyclooxygenase (COX-1) and the inducible form (COX-2); the specimens from 14 patients included normal breast tissue.
We determined COX-1 and COX-2 expression, and the corresponding PGE2 secretions, in 4 ER-negative human breast cancer cell lines, the MCF10A breast epithelial cell line, and the same non-cancerous line transfected with a mutated ras gene.
In this study we investigated whether expression of the inducible isoform of Cox (Cox-2) is linked with the multidrug resistance phenotype in breast cancer.
Over-expression of the arachidonic acid-metabolizing enzymes cyclooxygenase-2 and lypoxygenases is frequently observed in breast cancer, particularly the non-estrogen-responsive type, suggesting a role of the arachidonic acid (AA) cascade in the growth regulation of these malignancies.
These results strengthen the rationale for developing clinical trials to determine whether selective Cox-2 inhibitors possess anticancer properties in humans at risk for breast cancer.
Studies from mouse models of mammary tumorigenesis and from human breast cancer cell lines provide evidence that COX-2 overexpression plays an important role in the pathogenesis of malignant breast cancer in humans.
The prostaglandin PGE(2) increases intracellular cAMP levels and stimulates estrogen biosynthesis, and our recent studies have shown a strong linear association between CYP19 expression and the sum of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) expression in breast cancer specimens.
Aberrant upregulation of COX-2 enzyme resulting in accumulation of PGE2 in a cancer cell environment is a marker for progression of many cancers, including breast cancer.
The purpose of our study was to examine the relationship between COX-2 (with the resulting prostaglandins E(2), PGE(2)) and PPARgamma (and its natural endogenous ligand 15-Deoxy-Delta(12,14)-prostaglandin J(2), 15d-PGJ(2)) at various stages during the development of human breast cancer and its progression to metastasis.
The present study aims to compare COX-2 mRNA expression with hormone receptor status, S-phase fraction, telomerase activity, and DNA ploidy in human breast cancer.
Phosphocitrate inhibits calcium hydroxyapatite induced mitogenesis and upregulation of matrix metalloproteinase-1, interleukin-1beta and cyclooxygenase-2 mRNA in human breast cancer cell lines.
In the current study, we have determined that expression of both COX-2 mRNA and CUGBP2 mRNA are induced in MCF-7 cells, a breast cancer cell line, following exposure to 12 Gy gamma-irradiation.
This study shows that human breast tumours aberrantly express lipoxygenases and cyclooxygenase-2 and that decreased level of 15-lipoxygenase and raised level of cyclooxygenase-2 and 12-lipoxygenase has prognostic value in patients with breast cancer.
Reduced T-cell and dendritic cell function is related to cyclooxygenase-2 overexpression and prostaglandin E2 secretion in patients with breast cancer.
To investigate a possible contribution of dysregulation of mRNA stability to the progression of cancer and to overexpression of COX-2, we studied expression of HuR in 208 primary breast carcinomas by immunohistochemistry.
Since both COX-2 and iNOS are implicated in breast cancer progression, our findings of EP(4) receptor-mediated upregulation of iNOS in COX-2-expressing breast cancer cells suggest that blocking COX-2 and/or EP(4) may provide a simple therapeutic modality in this tumor model.
Thus, RXR-selective retinoids that inhibit AP-1 activity and suppress COX-2 expression may be particularly promising drugs for breast cancer prevention.
This review focuses on the molecular targeting compounds directed against the known molecular pathways involved in breast cancer such as: type I growth factors (HER-2/neu; epidermal growth factor receptor [EGFR]), angiogenesis, cyclooxigenase-2 (COX-2) and farnesylation.
To determine whether COX-2 induces drug resistance, plasmids encoding the COX-2 gene were stably transfected into ERalpha-positive MCF-7 human breast cancer cells (MCF-7/COX-2).
While COX-2 expression in normal breast epithelium in vivo has not been proven to be linked to an increased risk of breast cancer, its over-expression in the premalignant model in vitro does provide preliminary evidence that COX-2 inhibition may be a useful chemoprevention strategy.