Oestrogen receptor-alpha contributes to the regulation of the hedgehog signalling pathway in ERalpha-positive gastric cancer.
Oestrogen receptor-alpha contributes to the regulation of the hedgehog signalling pathway in ERalpha-positive gastric cancer.
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DOI：
10.1038/sj.bjc.6605517
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发表时间：
2010-02-16
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
雌激素受体α（ERα）在弥漫型胃癌中高表达，雌激素可促进ERα阳性胃癌的增殖。然而，雌激素增加这些细胞增殖的详细机制仍不清楚。我们使用17-β-雌二醇（E2）作为ERα通路的刺激剂。用纯的抗雌激素药物ICI 182 780（ICI）和针对ERα的小干扰RNA（ERα siRNA）作为抑制剂。环巴胺（Cyc）被用作Hedgehog（Hh）通路抑制剂。以两株ERα阳性的人胃癌细胞为靶细胞。还检测了刺激剂和抑制剂对E2诱导的细胞增殖的影响。在ERα阳性细胞中，E2不仅增加细胞增殖，而且增加Hh通路的配体之一Shh的表达。ICI、ERα siRNA和Cyc均能抑制17-β-雌二醇诱导的细胞增殖。ICI和ERα siRNA可抑制E2诱导的Shh表达增加，而Cyc则无此作用。此外，重组Shh激活Hh通路并增加细胞增殖，而抗Shh抗体抑制E2诱导的细胞增殖。当使用手术切除的胃癌标本分析ERα和Shh表达之间的关系时，发现正相关，表明ERα和Hh通路之间存在联系。我们的数据表明，ERα通路的激活通过以配体依赖性方式激活Hh通路，通过Shh诱导ERα阳性胃癌来促进细胞增殖。
Oestrogen receptor-alpha (ERα) is highly expressed in diffuse-type gastric cancer and oestrogen increases the proliferation of ERα-positive gastric cancer. However, a detailed mechanism by which oestrogen increases the proliferation of these cells is still unclear. We used 17-β-oestradiol (E2) as a stimulator against the ERα pathway. Pure anti-oestrogen drug ICI 182 780 (ICI) and small interfering RNA against ERα (ERα siRNA) were used as inhibitors. Cyclopamine (Cyc) was used as the hedgehog (Hh) pathway inhibitor. Two human ERα-positive gastric cancer cells were used as target cells. Effects of the stimulator and inhibitor on E2-induced cell proliferation were also examined. In ERα-positive cells, E2 increased not only cell proliferation but also one of the ligands of the Hh pathway, Shh expression. 17-β-Oestradiol-induced cell proliferation was suppressed by ICI, ERα siRNA or Cyc. The increased expression of Shh induced by E2 was suppressed by ICI and ERα siRNA but not by Cyc. Furthermore, recombinant Shh activated the Hh pathway and increased cell proliferation, whereas anti-Shh antibody suppressed E2-induced cell proliferation. When a relationship between ERα and Shh expressions was analysed using surgically resected gastric cancer specimens, a positive correlation was found, suggesting a linkage between the ERα and Hh pathways. Our data indicate that activation of the ERα pathway promotes cell proliferation by activating the Hh pathway in a ligand-dependent manner through Shh induction of ERα-positive gastric cancer.
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DOI：
10.1111/apm.1965.64.1.31
发表时间：
1965-01-01
期刊：
ACTA PATHOLOGICA ET MICROBIOLOGICA SCANDINAVICA
影响因子：
--
作者：
LAUREN, P
通讯作者：
LAUREN, P
DOI：
10.1006/bbrc.1997.7683
发表时间：
1997-11-17
影响因子：
3.1
作者：
CampbellThompson, ML
通讯作者：
CampbellThompson, ML
影响因子：
4.8
作者：
Kato, K;Horiuchi, S;Wake, N
通讯作者：
Wake, N
影响因子：
11.2
作者：
Kubo, M;Nakamura, M;Katano, M
通讯作者：
Katano, M
影响因子：
64.8
作者：
Karhadkar, SS;Bova, GS;Beachy, PA
通讯作者：
Beachy, PA