TY - JOUR
T1 - Inhibitory effects of ERβ on proliferation, invasion, and tumor formation of MCF-7 breast cancer cells-prognostication for the use of ERβ-selective therapy
AU - Li, Hui
AU - Tu, Zhenzhen
AU - An, Lianxiao
AU - Qian, Zhiyu
AU - Achilefu, Samuel
AU - Gu, Yueqing
N1 - Funding Information:
The study was supported by Natural Science Foundation Committee (NSFC 30672015, 30700779, 30800257, 30970776) and the major project from the Ministry of Science and Technology for new drug development (2009ZX09310-004).
PY - 2012/7
Y1 - 2012/7
N2 - Context: Estrogen is well-known as an important factor in the physiological functions and pathological processes of breast. Estrogen receptor β (ERβ) is expressed in the majority of breast cancers at lower levels compared with the normal breast tissue. Objective: The effect of ERβ on the characteristics of breast tumor cells and its prognostication for the use of ERβ-selective therapy were investigated here for the first time. Materials and methods: ERβ was overexpressed in ERα positive MCF-7 breast cancer cells by gene transfection. The proliferation, motility, and xenografts growth of MCF-7 cells were investigated by MTT assays, wound-healing assay and animal study. Results: Results demonstrated that ERβ-GFP localized in both the cytoplasm and the nucleus in the presence of 17β-estradiol (E2), with stronger fluorescence-signal intensity in the nucleus, 2.8-times higher than that in the cytoplasm. The ERβ overexpressed MCF-7 cells resulted in a 38.7% decreased growth rate and motility in vitro. Furthermore, ERβ overexpression enhanced the antiproliferative effects of phytoestrogen, antiestrogen, and histone deacetylase inhibitor. Exogenous ERβ expression reduced tumor volume by 99% at 27 days postadministration, indicated that overexpression of ERβ led to retardation of tumor formation and growth in immunodeficient mice. Discussion and conclusion: This study provided a relatively new evidence to support that ERβ is an important modulator of proliferation and motility of breast cancer cells, and implied for the first time a possibility for the use of novel ERβ-selective therapies in breast cancer treatment.
AB - Context: Estrogen is well-known as an important factor in the physiological functions and pathological processes of breast. Estrogen receptor β (ERβ) is expressed in the majority of breast cancers at lower levels compared with the normal breast tissue. Objective: The effect of ERβ on the characteristics of breast tumor cells and its prognostication for the use of ERβ-selective therapy were investigated here for the first time. Materials and methods: ERβ was overexpressed in ERα positive MCF-7 breast cancer cells by gene transfection. The proliferation, motility, and xenografts growth of MCF-7 cells were investigated by MTT assays, wound-healing assay and animal study. Results: Results demonstrated that ERβ-GFP localized in both the cytoplasm and the nucleus in the presence of 17β-estradiol (E2), with stronger fluorescence-signal intensity in the nucleus, 2.8-times higher than that in the cytoplasm. The ERβ overexpressed MCF-7 cells resulted in a 38.7% decreased growth rate and motility in vitro. Furthermore, ERβ overexpression enhanced the antiproliferative effects of phytoestrogen, antiestrogen, and histone deacetylase inhibitor. Exogenous ERβ expression reduced tumor volume by 99% at 27 days postadministration, indicated that overexpression of ERβ led to retardation of tumor formation and growth in immunodeficient mice. Discussion and conclusion: This study provided a relatively new evidence to support that ERβ is an important modulator of proliferation and motility of breast cancer cells, and implied for the first time a possibility for the use of novel ERβ-selective therapies in breast cancer treatment.
KW - Estrogen receptor β
KW - GFP
KW - breast cancer
KW - stable transfection
KW - xenograft
UR - http://www.scopus.com/inward/record.url?scp=84861998607&partnerID=8YFLogxK
U2 - 10.3109/13880209.2011.637506
DO - 10.3109/13880209.2011.637506
M3 - Article
C2 - 22486657
AN - SCOPUS:84861998607
VL - 50
SP - 839
EP - 849
JO - Pharmaceutical Biology
JF - Pharmaceutical Biology
SN - 1388-0209
IS - 7
ER -