Zang Xiao-Ping, Pento J Thomas
Department of Pharmaceutical Sciences, College of Pharmacy, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73117, USA.
Anticancer Res. 2008 Sep-Oct;28(5A):2733-5.
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.
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.
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.
ER-alpha expression is associated with KGF-induced proliferation of breast cancer cells.
角质形成细胞生长因子(KGF)可使雌激素受体(ER)阳性乳腺癌细胞的增殖和运动能力迅速增强,而雌激素剥夺和/或抗雌激素治疗可消除这种作用。本研究使用小干扰RNA(siRNA)选择性抑制ER-α表达,检验了ER-α参与MCF-7癌细胞中KGF增殖的假说。
在转染ER-α siRNA 48小时后,用KGF(50 ng/ml)或赋形剂处理MCF-7细胞24小时。使用MTT法测量细胞增殖。通过蛋白质印迹法定量ER-α蛋白水平。
ER-α siRNA转染显著降低了ER-α表达和MCF-7细胞增殖。在转染siRNA的MCF-7细胞中,KGF介导的细胞增殖增强和运动细胞形态减少或消失。
ER-α表达与KGF诱导的乳腺癌细胞增殖相关。