Retinoic acid mediates regulation of network formation by COUP-TFII and VE-cadherin expression by TGFbeta receptor kinase in breast cancer cells.
Retinoic acid mediates regulation of network formation by COUP-TFII and VE-cadherin expression by TGFbeta receptor kinase in breast cancer cells.
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DOI：
10.1371/journal.pone.0010023
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发表时间：
2010-04-06
期刊：
影响因子：
3.7
通讯作者：
Byers SW
中科院分区：
文献类型：
--
作者：
Prahalad P;Dakshanamurthy S;Ressom H;Byers SW
肿瘤的发展、生长和转移依赖于充足的血管供应。这可能是由于血管生成的调节，循环内皮祖细胞的募集，和/或血管转分化。我们之前的研究表明，维甲酸（RA）治疗将一部分乳腺癌细胞转化为具有显著内皮基因型和表型元素的细胞，包括ve -钙粘蛋白的显著诱导，这是导致部分但不是全部形态变化的原因。本研究表明，在RA治疗诱导的内皮相关基因中，只有少数受到VE-cadherin敲低的影响，排除了VE-cadherin作为RA诱导的内皮基因型开关的调节因子的可能性。相反，敲低ra诱导的基因COUP-TFII可以阻止基质细胞网络的形成，但对VE-cadherin诱导或细胞融合没有影响。两种泛激酶抑制剂明显阻断ra诱导的VE-cadherin表达和细胞融合。然而，RA治疗导致酪氨酸激酶活性显著而广泛的降低。RA可诱导TGFβ信号通路中的多个基因，特异性抑制TGFβ I型受体可阻断RA诱导的VE-cadherin表达和细胞融合。综上所述，这些数据表明tgf - β途径和COUP-TFII在介导RA内皮转分化特性中的作用。
Tumor development, growth, and metastasis depend on the provision of an adequate vascular supply. This can be due to regulated angiogenesis, recruitment of circulating endothelial progenitors, and/or vascular transdifferentiation. Our previous studies showed that retinoic acid (RA) treatment converts a subset of breast cancer cells into cells with significant endothelial genotypic and phenotypic elements including marked induction of VE-cadherin, which was responsible for some but not all morphological changes. The present study demonstrates that of the endothelial-related genes induced by RA treatment, only a few were affected by knockdown of VE-cadherin, ruling it out as a regulator of the RA-induced endothelial genotypic switch. In contrast, knockdown of the RA-induced gene COUP-TFII prevented the formation of networks in Matrigel but had no effect on VE-cadherin induction or cell fusion. Two pan-kinase inhibitors markedly blocked RA-induced VE-cadherin expression and cell fusion. However, RA treatment resulted in a marked and broad reduction in tyrosine kinase activity. Several genes in the TGFβ signaling pathway were induced by RA, and specific inhibition of the TGFβ type I receptor blocked both RA-induced VE-cadherin expression and cell fusion. Together these data indicate a role for the TGFβ pathway and COUP-TFII in mediating the endothelial transdifferentiating properties of RA.
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影响因子：
3.6
作者：
Hess, AR;Seftor, EA;Hendrix, MJC
通讯作者：
Hendrix, MJC
影响因子：
11.4
作者：
Goumans, MJ;Valdimarsdottir, G;ten Dijke, P
通讯作者：
ten Dijke, P
DOI：
10.1080/10623320600903940
发表时间：
2006-07-01
影响因子：
--
作者：
Piao, Meihua;Mori, Daisuke;Tokunaga, Osamu
通讯作者：
Tokunaga, Osamu
影响因子：
4
作者：
Gifford, SM;Grummer, MA;Bird, IM
通讯作者：
Bird, IM
影响因子：
19.6
作者：
Nakagawa, T;Li, JH;Johnson, RJ
通讯作者：
Johnson, RJ