Estrogen receptor α variant ERα46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17β-oestradiol
Estrogen receptor α variant ERα46 mediates growth inhibition and apoptosis of human HT-29 colon adenocarcinoma cells in the presence of 17β-oestradiol
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DOI：
10.1097/00029330-200806010-00012
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发表时间：
2008-06-05
影响因子：
6.1
通讯作者：
Teng Li-song
中科院分区：
文献类型：
--
作者：
Jiang Hai-ping;Teng Rong-yue;Teng Li-song
背景雌激素参与抑制结肠癌的发展，并通过雌激素受体α和β（ER α，ER β）发挥其功能。最近确定的ER α 46导致外显子1缺失的66 kDa的全长形式的ER α 66是缺乏反式激活结构域AF-1，其功能仍然在很大程度上unknowed.Methods在这项研究中，我们比较了ER α 46 mRNA的表达在32例正常大肠组织和其匹配的大肠癌组织的实时定量聚合酶链反应（PCR）。用ER α 46表达载体转染内源性低表达ER α 46的人结肠腺癌细胞HT-29;甲基噻唑基四唑（MTT）测定，流式细胞术，DNA片段化和TUNEL染色用于评估细胞在17 β-葡聚糖存在下的增殖和凋亡状态。结果ER α 46 mRNA在正常大肠组织中的表达明显高于癌组织。10（-8）mol/L17 β-雌二醇处理后，ER α 46转染细胞的生长速度明显低于对照细胞，G（0/1）期细胞增多，G（2）/M期细胞比例减少。结论ER α 46可能通过介导17 β雌二醇对大肠癌细胞的生长抑制和凋亡而参与大肠癌的发生和/或发展。
Background Estrogen is involved in suppression of colon cancer development and exerts its function via estrogen receptors alpha and beta (ER alpha, ER beta). The recently identified ER alpha 46 resulted from exon 1-deletion from the 66-kDa full length form of ER alpha 66 is devoid of the transactivation domain AF-1, whose function remains largely unknown.Methods In this study, we compared the expression of ERa46 mRNA in 32 normal colorectal tissues and their matched colorectal cancer tissues by real-time quantitative polymerase chain reaction (PCR). Human colon adenocarcinoma cell HT-29, that has low endogenous expression of ERa46, was transfected with ER alpha 46-expression vector; methyl thiazolyl tetrazolium (MTT) assay, flow cytometry, DNA fragmentation and TUNEL staining were used to evaluate the proliferation and apoptosis status of the cells in the presence of 17 beta-oestradiol.Results Higher ERa46 mRNA levels were observed in normal colorectal tissues than in the corresponding cancer tissues. ER alpha 46-transfected cells showed a significantly decreased growth rate than control cells and an accumulation of cells in the G(0/1) phase and a reduced proportion of cells in G(2)/M phase after exposed to 10(-8) mol/L 17 beta-oestradiol. There were also more positive TUNEL stained cells in ERa46-transfected cells than the control cells in the presence of 17 beta-oestradiol (P < 0.05).Conclusions These data suggest that ER alpha 46 may be involved in the development and/or progression of colorectal cancer via mediating growth inhibition and apoptosis of cancer cells in the presence of 17 beta-oestradiol.