Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity.
Resistance to ursodeoxycholic acid-induced growth arrest can also result in resistance to deoxycholic acid-induced apoptosis and increased tumorgenicity.
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DOI：
10.1186/1471-2407-6-219
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发表时间：
2006-09-01
期刊：
影响因子：
3.8
通讯作者：
Martinez JD
中科院分区：
文献类型：
--
作者：
Powell AA;Akare S;Qi W;Herzer P;Jean-Louis S;Feldman RA;Martinez JD
有大量证据表明胆汁酸增加结肠癌的风险并作为肿瘤促进剂，然而，胆汁酸介导的肿瘤发生的机制尚不清楚。以前，我们表明，脱氧胆酸（DCA），致肿瘤的胆汁酸，熊去氧胆酸（UDCA），一个假定的化学预防剂，表现出不同的生物学效应，但似乎对一些相同的信号分子。本研究旨在确定致瘤胆汁酸DCA和化学预防胆汁酸UDCA激活的信号通路是否存在重叠。为了确定DCA和UDCA对信号通路的激活是否存在重叠，我们对HCT 116细胞进行诱变，然后分离出对UDCA诱导的生长停滞具有抗性的细胞系。然后测试这些细胞系对DCA诱导的细胞凋亡的响应。我们发现，大多数对UDCA诱导的生长停滞具有抗性的细胞系也对DCA诱导的细胞凋亡具有抗性，这意味着DCA和UDCA介导的信号传导存在重叠。此外，对DCA诱导的凋亡最具抗性的细胞系也表现出更大的锚定非依赖性生长能力。我们的结论是UDCA和DCA具有重叠的信号传导活性，这些通路的失调可导致更晚期的肿瘤表型。
There is a large body of evidence which suggests that bile acids increase the risk of colon cancer and act as tumor promoters, however, the mechanism(s) of bile acids mediated tumorigenesis is not clear. Previously we showed that deoxycholic acid (DCA), a tumorogenic bile acid, and ursodeoxycholic acid (UDCA), a putative chemopreventive agent, exhibited distinct biological effects, yet appeared to act on some of the same signaling molecules. The present study was carried out to determine whether there is overlap in signaling pathways activated by tumorogenic bile acid DCA and chemopreventive bile acid UDCA. To determine whether there was an overlap in activation of signaling pathways by DCA and UDCA, we mutagenized HCT116 cells and then isolated cell lines resistant to UDCA induced growth arrest. These lines were then tested for their response to DCA induced apoptosis. We found that a majority of the cell lines resistant to UDCA-induced growth arrest were also resistant to DCA-induced apoptosis, implying an overlap in DCA and UDCA mediated signaling. Moreover, the cell lines which were the most resistant to DCA-induced apoptosis also exhibited a greater capacity for anchorage independent growth. We conclude that UDCA and DCA have overlapping signaling activities and that disregulation of these pathways can lead to a more advanced neoplastic phenotype.
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影响因子：
3.3
作者：
Qiao, L;Studer, E;Dent, P
通讯作者：
Dent, P
影响因子：
2.9
作者：
Im, E;Akare, S;Martinez, JD
通讯作者：
Martinez, JD
影响因子：
4.1
作者：
Powell, AA;LaRue, JM;Martinez, JD
通讯作者：
Martinez, JD
DOI：
10.1016/0165-1110(90)90023-5
发表时间：
1990-05-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
HILL, MJ
通讯作者：
HILL, MJ
影响因子：
4.1
作者：
Kanda, T;Foucand, L;Fujii, H
通讯作者：
Fujii, H