Tazarotene-induced gene 1 inhibits prostaglandin E2-stimulated HCT116 colon cancer cell growth.
Tazarotene-induced gene 1 inhibits prostaglandin E2-stimulated HCT116 colon cancer cell growth.
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DOI：
10.1186/1423-0127-18-88
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发表时间：
2011-11-30
影响因子：
11
通讯作者：
Jiang SY
中科院分区：
文献类型：
--
作者：
Tsai FM;Wu CC;Shyu RY;Wang CH;Jiang SY
他扎罗汀诱导基因1（TIG 1）是一个假定的肿瘤抑制基因。我们最近已经证明TIG 1A和TIG 1B同种型抑制细胞生长，并诱导G蛋白偶联受体激酶5（GRK 5）在结肠癌细胞中的表达。由于升高的前列腺素E2（PGE 2）信号在结直肠癌发生中起重要作用，本研究的目的是探讨TIG 1对PGE 2诱导的结肠癌细胞增殖和信号传导的影响。使用HCT 116细胞以及使用GeneSwitch系统从HCT 116结肠癌细胞建立的TIG 1A和TIG 1B稳定细胞。在稳定的细胞中，米非司酮处理诱导TIG 1亚型表达。使用WST-1细胞增殖试验测定细胞生长。β-连环蛋白/TCF和环磷酸腺苷（cAMP）/CREB信号通路的激活使用荧光素酶报告基因测定。Western blot和共聚焦显微镜分析β-catenin的表达和亚细胞分布。使用酶免疫测定法测量cAMP水平。RNA干扰被用来检查TIG 1和GRK 5介导的变化的影响。在诱导型TIG 1A-和TIG 1B-稳定的HCT 116细胞中，PGE 2刺激的细胞生长减少。GRK 5表达被TIG 1A和TIG 1B同种型上调，并且其表达抑制PGE 2刺激的HCT 116细胞生长。GRK 5、TIG 1A和TIG 1B表达显著抑制PGE 2刺激的β-catenin/TCF和cAMP信号通路报告基因和cAMP。此外，PGE 2刺激的β-连环蛋白的核定位被TIG 1A和TIG 1B的表达抑制，这被TIG 1和GRK 5 siRNA改善。TIG 1通过GRK 5抑制结肠癌细胞中PGE 2刺激的Wnt和cAMP信号通路。
The tazarotene-induced gene 1 (TIG1) is a putative tumor suppressor gene. We have recently demonstrated both TIG1A and TIG1B isoforms inhibited cell growth and induced the expression of G protein-coupled receptor kinase 5 (GRK5) in colon cancer cells. Because elevated prostaglandin E2 (PGE2) signaling plays a significant role in colorectal carcinogenesis, the objective of this study was to explore the effect of TIG1 on PGE2-induced cellular proliferation and signaling in colon cancer cells. HCT116 cells as well as TIG1A and TIG1B stable cells established from HCT116 colon cancer cells using the GeneSwitch system were used. TIG1 isoform expression was induced by mifepristone treatment in stable cells. Cell growth was determined using the WST-1 cell proliferation assay. Activation of β-catenin/TCF and cyclic adenosine monophosphate (cAMP)/CREB signaling pathways were determined using luciferase reporter assays. Expression and subcellular distribution of β-catenin were analyzed using Western blot and confocal microscope. Levels of cAMP were measured using an enzyme immunoassay. RNA interference was used to examine the effects of TIG1- and GRK5-mediated changes. PGE2-stimulated cell growth was reduced in inducible TIG1A- and TIG1B-stable HCT116 cells. GRK5 expression was upregulated by both TIG1A and TIG1B isoforms, and its expression suppressed PGE2-stimulated HCT116 cell growth. GRK5, TIG1A, and TIG1B expression significantly inhibited PGE2-stimulated β-catenin/TCF and cAMP signaling pathway reporters and cAMP. Also, PGE2-stimulated nuclear localization of β-catenin was inhibited by expression of TIG1A and TIG1B, which was ameliorated by both TIG1 and GRK5 siRNAs. TIG1 suppressed PGE2-stimulated Wnt and cAMP signaling pathways in colon cancer cells through GRK5.
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影响因子：
6.4
作者：
Kwong, J;Lo, KW;Huang, DP
通讯作者：
Huang, DP
影响因子：
8
作者：
Sekine, S;Shibata, T;Hirohashi, S
通讯作者：
Hirohashi, S
DOI：
10.1016/j.bbrc.2004.09.025
发表时间：
2004-11-05
影响因子：
3.1
作者：
Miyashiro, M;Furuya, S;Sugita, T
通讯作者：
Sugita, T
影响因子：
8.5
作者：
Ohnishi, S.;Okabe, K.;Nagaya, N.
通讯作者：
Nagaya, N.
影响因子：
4.3
作者：
Rambow, F.;Malek, O.;Vincent-Naulleau, S.
通讯作者：
Vincent-Naulleau, S.