The impact of Catechol-O-methyl transferase knockdown on the cell proliferation of hormone-responsive cancers
Tolba, Mai; Omar, Hany A; Hersi, Fatima; Nunes, Ane C F; Noreddin, Ayman M;
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, p21cip1, p27kip1, 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.
Other data
Title | The impact of Catechol-O-methyl transferase knockdown on the cell proliferation of hormone-responsive cancers | Authors | Tolba, Mai ; Omar, Hany A; Hersi, Fatima; Nunes, Ane C F; Noreddin, Ayman M | Keywords | Breast cancer;Prostate cancer;Tumor suppressor;Catechol-O-methyl transferase (COMT) | Issue Date | 15-May-2019 | Journal | Molecular and cellular endocrinology | Volume | 488 | Start page | 79 | End page | 88 | ISSN | 03037207 | DOI | 10.1016/j.mce.2019.03.007 | PubMed ID | 30904591 | Scopus ID | 2-s2.0-85063546544 |
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