The impact of Catechol-O-methyl transferase knockdown on the cell proliferation of hormone-responsive cancers. (15th May 2019)

• Record Type: Journal Article
• Authors: Tolba, Mai F.; Omar, Hany A.; Hersi, Fatima; Nunes, Ane C.F.; Noreddin, Ayman M.
• Is Part Of: Molecular and cellular endocrinology. Volume 488(2019)
• Page Start: 79
• Page End: 88
• Publication Date: 2019-05-15
• Subjects: Catechol-O-methyl transferase (COMT) -- Breast cancer -- Prostate cancer -- Proliferation -- Tumor suppressor; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.03.007
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: Estrogen (E2) plays a central role in the development and progression of hormone-responsive cancers. Estrogen metabolites exhibit either stimulatory or inhibitory roles on breast and prostate cells. The catechol metabolite 4-hydroxyestradiol (4-OHE2) enhances cell proliferation, while 2-methoxyestradiol (2 ME) possesses anticancer activity. The major metabolizing enzyme responsible for detoxifying the deleterious metabolite 4-OHE2 and forming the anticancer metabolite 2 ME is Catechol-O-Methyl Transferase (COMT). The current work investigated the relationship between the expression level of COMT and the cell proliferation of hormone-responsive cancers. The results showed that COMT silencing enhanced the cell proliferation of ER-α positive cancer cells MCF-7 and PC-3 but not the cells that lack ER-α expression as MDA-MB231 and DU-145. The data generated from our study provides a better understanding of the effect of COMT on critical signaling pathways involved in the development and progression of breast cancer (BC) and prostate cancer (PC) including ER-α, p21 cip1, p27 kip1, NF-κB (P65) and CYP19A1. These findings suggest that COMT enzyme plays a tumor suppressor role in hormone receptor-positive tumors which opens the door for future studies to validate COMT expression as a novel biomarker for the prediction of cancer aggressiveness and treatment efficacy. Graphical abstract: Image 1 Highlights: COMT silencing enhanced the cell proliferation of ER-α positive cancer cells. The decreased activity of COMT enhanced ER-α and NF-kB signaling pathways. The expression of p27 kip1 and aromatase were COMT-dependent. COMT enzyme plays a tumor suppressor role in hormone receptor-positive tumors. Cancer aggressiveness can be predicted through COMT expression levels.