Stable knockdown of estrogen receptor alpha by vector-based RNA interference suppresses proliferation and enhances apoptosis in breast cancer cells.
Breast cancer, the most common malignancy in women, has a known association with the steroid hormone estrogen. Estrogen receptor alpha (ERalpha) plays an important role in the clinical care of breast cancer patients, both as a prognostic factor and as a therapeutic target. Here, we show that a small interfering RNA (siRNA) against ERalpha downregulates ERalpha expression in human MCF-7 and Bcap-37 breast cancer cells, causing a significant decrease in breast cancer cell proliferation. Tumor cells lacking ERalpha expression grew at a much slower rate than did control cells in vitro. Moreover, ERalpha knockdown in breast cancer cells resulted in decreased, even completely abrogated tumor growth in BALB/c nude mice, providing direct evidence for an essential role of ERalpha in breast cancer growth. Our results suggest siRNA-mediated gene silencing of ERalpha may impair tumorigenicity, and even suppress the tumor growth.
Fu
Hai-Jing
HJ
State Key Laboratory of Cancer Biology, Department of Biochemistry and Molecular Biology, Fourth Military Medical University, Xi'an, China.
Jia
Lin-Tao
LT
Bao
Wei
W
Zhao
Jing
J
Meng
Yan-Ling
YL
Wang
Cheng-Ji
CJ
Yao
Li-Bo
LB
Chen
Si-Yi
SY
Yang
An-Gang
AG
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering