Sayer Ji
Founder of GreenMedInfo.com

Sign up for our Free Newsletter

A Community of 200,000+ Subscribers benefit from our latest research and news.

Abstract Title:

Melatonin suppresses aromatase expression and activity in breast cancer associated fibroblasts.

Abstract Source:

Breast Cancer Res Treat. 2012 Apr ;132(2):765-71. Epub 2012 Jan 12. PMID: 22237979

Abstract Author(s):

Kevin C Knower, Sarah Q To, Kiyoshi Takagi, Yasuhiro Miki, Hironobu Sasano, Evan R Simpson, Colin D Clyne

Article Affiliation:

Cancer Drug Discovery Laboratory, Prince Henry's Institute of Medical Research, PO Box 5152, Clayton, VIC 3168, Australia. kevin.knower@princehenrys.org

Abstract:

The main biological active substance secreted by the pineal gland, melatonin (MLT), counteracts the effects of estrogens in breast cancer via exerting a number of its own oncostatic properties. Recent studies of postmenopausal women have identified that the major metabolite of MLT is statistically significantly associated with a lower risk of developing breast cancer. While MLT production decreases with age, breast cancer risk, however, increases with age and obesity. We hypothesize that MLT inhibits estrogen production in breast adipose fibroblasts (BAFs), the main local source of estrogen in breast tumors of postmenopausal women, by inhibiting transcription of the CYP19A1 gene that encodes the key enzyme aromatase. Normal BAFs were cultured from women undergoing breast reduction surgery, while breast cancer-associated fibroblasts (CAFs) were isolated from three women with estrogen receptor (ER) positive invasive ductal carcinomas. MTNR1A and MTNR1B receptor expression and CYP19A1 mRNA expression following MLT treatments were determined by qRT-PCR. BAFs express the G-protein coupled MLT receptors MTNR1A and MTNR1B with elevated levels of MTNR1A found in CAFs. Treatment of BAFs and CAFs with MLT resulted in significant suppression of CYP19A1 transcription and aromatase activity at pharmacological, physiological and sub-physiological concentrations. MLT suppression occurred through promoter-specific PI.4-, PI.3- and PII-derived CYP19A1 mRNA. Stimulation of CYP19A1 PII-mRNA and aromatase activity by prostaglandin E(2) (PGE(2)) were significantly attenuated by physiological doses of MLT. Lower levels of MLT in aging women may increase the risk of progressing ER-positive breast cancer through a decreased ability to suppress CYP19A1 expression and subsequent local estrogen production in BAFs/CAFs.

Study Type : In Vitro Study

Print Options


Key Research Topics

Popular Threads

Sayer Ji
Founder of GreenMedInfo.com

Sign up for our Free Newsletter

A Community of 200,000+ Subscribers benefit from our latest research and news.

This website is for information purposes only. By providing the information contained herein we are not diagnosing, treating, curing, mitigating, or preventing any type of disease or medical condition. Before beginning any type of natural, integrative or conventional treatment regimen, it is advisable to seek the advice of a licensed healthcare professional.

© Copyright 2008-2017 GreenMedInfo.com, Journal Articles copyright of original owners, MeSH copyright NLM.