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Differential Regulatory Effects of Nitric Oxide on Estrogen Stimulated MCF7 Breast Cancer Cell Growth
Author(s) -
Chan Robbie,
Wong Mansau,
Lo Samuel
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a979-b
Subject(s) - cell growth , nitric oxide , estrogen , estrogen receptor , fetal bovine serum , cell culture , chemistry , endocrinology , in vitro , medicine , stimulation , cell , biology , breast cancer , cancer , biochemistry , genetics
17‐β estradiol (E 2 ) stimulates the growth of estrogen receptor (ER)positive cells such as MCF7 line of human breast cancer cells. There have been reports showing E 2 affects the level of endothelial nitric oxide synthase (eNOS) expression and its activity in vitro. Using ER positive MCF7 breast cancer cells as a model, we have studied the relationship between E 2 and NO in controlling cell growth. MCF7 cells were cultured in medium containing 5% charcoal‐stripped fetal bovine serum (SFBS) or serum‐free medium (SFM) respectively. Using [methyl‐ 3 H]thymidine incorporation as the growth assay, E 2 stimulated cell growth in a dose‐response manner under both conditions. In the presence of 5 mM N‐nitro‐L‐arginine methyl ester (L‐NAME), an inhibitor of NOS, an enhancement of E 2 stimulation on MCF7 cell growth of up to 2 folds was observed when cultured with 5% SFBS, however, it completely blocked the stimulatory effect of E 2 on cell growth under serum‐free condition. Fluorescent agent DAF‐2A was used to measure NO production by MCF7 cells under different treatments. We found 1 nM E 2 decreased NO production by 50% compared with untreated cells in 5% SFBS but did not significantly change NO production under serum‐free condition. 5 mM L‐NAME suppressed NO production in all conditions below their respective untreated control level. Our data show that in spite of the stimulatory effect of E 2 on MCF7 cell growth, there is a differential regulation of NO production by E 2 under different culture conditions and NO in turn differentially regulates the growth activity of breast cancer cells.