Abstract 4599: Bile acids modulate estrogen receptor β signaling through nongenomic actions in colorectal cancer

• Published in: Cancer research (Chicago, Ill.) Ill.), 2016-07, Vol.76 (14_Supplement), p.4599-4599
• Main Author: Trujillo, Jesse
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2016-4599

Bile acids deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA) have contrasting effects on tumor development. DCA is measurable at increased levels in the serum of colorectal adenocarcinoma patients and is associated with disease progression. DCA is also a well-established tumor promoter. On the other hand, UDCA is a chemopreventative agent revealed to suppress the recurrence of highly dysplastic polyps in a phase III clinical trial. Remarkably, retrospective investigation of the data had shown that UDCA's efficacy as a chemopreventive mediator was gender specific. UDCA significantly lowered the recurrence of advanced lesions in males, but caused a significant increase in the recurrence of advanced lesions in females. Our lab is in pursuit of understanding the gender specific chemopreventive role of UDCA. Estrogen receptor β (ERβ) has been shown to play a significant role in controlling the development of colorectal cancer. Therefore, we hypothesized that the altered regulation of the ERβ pathway by UDCA might explain the gender specificity of this molecule. In order to assess this, we analyzed the effects of UDCA on ERβ to those of the known tumor promoter DCA in both male and female human adenocarcinoma cell lines. Female HT-29 colorectal adenocarcinoma cells induced the phosphorylation of ERβ, as well as up-regulated gene expression of estrogen response elements (EREs), showing stimulated activity of this hormonal receptor. Moreover, we found that pre-treating the cells with PD98059, a MEK 1/2 inhibitor, UDCA and DCA-induced phosphorylation of ERβ, along with increased ERE gene expression, was significantly reduced. Collectively, this data suggests that UDCA and DCA can stimulate ERβ signaling through the non-genomic MAPK signaling cascade; suggesting that UDCA's gender-specific effects may be due, in part, to signaling through hormone receptors. Citation Format: Jesse Trujillo. Bile acids modulate estrogen receptor β signaling through nongenomic actions in colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4599.