SiRNA inhibition of ER-alpha expression reduces KGF-induced proliferation of breast cancer cells.
BACKGROUND
Keratinocyte growth factor (KGF) produces a rapid increase in the proliferation and motility of estrogen receptor (ER)-positive breast cancer cells which is abolished by estrogen deprivation and/or anti-estrogen treatment. The present study examined the hypothesis that ER-alpha is involved in the KGF proliferation in MCF-7 cancer cells using small interfering RNA (siRNA) to selectively inhibit ER-alpha expression.


METHODS
At 48 hours following ER-alpha siRNA transfection, the MCF-7 cells were treated with KGF (50 ng/ml) or vehicle for 24 hours. Cell proliferation was measured using a MTT assay. ER-alpha protein levels were quantified by Western blotting.


RESULTS
ER-alpha siRNA transfection significantly reduced ER-alpha expression and MCF-7 cell proliferation. KGF-mediated enhancement of cell proliferation and motile cell morphology were reduced or absent in the siRNA transfected MCF-7 cells.


CONCLUSIONS
ER-alpha expression is associated with KGF-induced proliferation of breast cancer cells.
Zang
Xiao-Ping
XP
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Pento
J Thomas
JT
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D051523:Fibroblast Growth Factor 7 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D034741:RNA, Small Interfering / Q000235:genetics*; D014162:Transfection
D047628:Estrogen Receptor alpha; D034741:RNA, Small Interfering; D051523:Fibroblast Growth Factor 7