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Regulation of COUP‐TFII expression in Tamoxifen‐ sensitive and resistant breast cancer cells.
Author(s) -
Cochrum Renate K.,
Riggs Krista A.,
Wickramasinghe Nalinie S.,
Klinge Carolyn M.
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.a968-c
Subject(s) - tamoxifen , estrogen receptor , cell growth , cancer research , breast cancer , cancer cell , medicine , agonist , cancer , endocrinology , estrogen , antiestrogen , mcf 7 , biology , receptor , biochemistry , human breast
Tamoxifen (TAM) is used for treatment and prevention of breast cancer. TAM competes with estradiol (E 2 ) in binding estrogen receptors α and β (ERα and ER β) inhibiting proliferation. However, initially TAM‐sensitive tumors become TAM‐resistant leading to metastases. The mechanism of TAM resistance is unknown and biomarkers of TAM‐response may be of use to monitor clinical response. One possible biomarker of TAM‐response is the orphan nuclear receptor COUP‐TFII which we found reduced in TAM‐resistant breast cancer. We determined the effects of serum, phenol red, E 2 , 4‐hydroxyTAM (4‐OHT), ICI 182,780 (ICI), and a phytoestrogen resveratrol on cell proliferation and COUP‐TFII expression in TAM‐ sensitive (MCF‐7 and LCC1) and resistant (LCC9 and LY2) cell lines. Results showed MCF‐7 and LCC1 cells are TAM‐sensitive, LCC9 and LY2 cells are resistant to TAM and ICI. Resveratrol inhibited proliferation in all cells. Reduced serum inhibited proliferation of TAM‐sensitive cells. Phenol red had estrogen agonist activity in a cell line‐specific manner. siRNA reduction of ERα in MCF‐7 cells did not affect COUP‐TFII expression, but PD98059 inhibited E 2 ‐induced COUP‐TFII expression. These results indicate COUP‐TFII expression is not dependent on ERα in MCF‐7 cells and suggest a possible role for ER β in regulating COUP‐TFII expression. Supported by Susan G. Komen Breast Cancer Foundation grant BCTR0201438 to CMK.