期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 488, 期 -, 页码 79-88出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2019.03.007
关键词
Catechol-O-methyl transferase (COMT); Breast cancer; Prostate cancer; Proliferation; Tumor suppressor
资金
- Fulbright scholarship (FY2015/2016)
- L'Oreal-UNESCO for Women in Science fellowship (Levant)
- L'Oreal-UNESCO for Women in Science fellowship (Egypt 2016)
- CNPq/Brazil Science Without Borders Program [201385202012-0]
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-alpha positive cancer cells MCF-7 and PC-3 but not the cells that lack ER-alpha 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-alpha, p21(cip1), p27(kip1), NF-kappa B (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.
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