title: Clinical relevance of cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MT1-MMP) in human breast cancer tissue.
abstract: Breast cancer (BC) is the most common neoplasm among women in most developed countries, including Egypt. Elevated levels of certain proteins in human BC are associated with unfavorable prognosis and progressive stages of the disease. The aim of our study was to evaluate the protein expression profile and prognostic significance of cyclooxygenase-2 (COX-2), matrix metalloproteinase-2 (MMP-2), MMP-9 and membrane type 1-MMP (MT1-MMP) and their interaction in operable BC patients. The protein expression of COX-2, MMP-2 and MT1-MMP were evaluated by western blot technique, whereas enzymatic activity of MMP-2 and MMP-9 was determined by zymography in 47 breast cancer patients as well as normal adjacent tissues. Also, the correlation between these proteins and age, tumor size, LN stage, TNM stage, estrogen receptor, progesterone receptor, disease-free survival, and overall survival (OS) has been investigated. As compared to adjacent normal tissues, COX-2, MMP-2 and MT1-MMP were over-expressed in 43, 64, and 60 % of tumor tissues, respectively. In the same pattern, the activity of MMP-2 (62 %) and MMP-9 (45 %) was elevated in BC tissues. Multivariate analysis showed a positive correlation between the protein expression of COX-2, MMP-2, and MT1-MMP and the activity of MMP-2 and MMP-9 in BC patients. However, the enzymatic activity showed no correlation with clinicopathological features. This study confirms the preclinical evidence that COX-2 increased the expression of MT1-MMP, which in turn activates MMP-2. The lack of correlation with clinicopathological features, OS or disease-free survival ascertains the complexity of tumor progression and metastasis with many pro- and counter regulatory factors.
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, 1 Kasr El-Aini St, Cairo, Egypt.
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Mohammad
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Zeeneldin
authors.forename: Zakaria Y
authors.initials: ZY
authors.lastname: Abd Elmageed
authors.forename: Ebtsam H
authors.initials: EH
authors.lastname: Khalil
authors.forename: Said M E
authors.initials: SM
authors.lastname: Mahdy
authors.forename: Hayat M
authors.initials: HM
authors.lastname: Sharada
authors.forename: Sabry K
authors.initials: SK
authors.lastname: Sharawy
authors.forename: Abdel-Hady A
authors.initials: AH
authors.lastname: Abdel-Wahab
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D047368:Tumor Burden
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14