The selective ERα antagonist could significantly decrease Wnt2b/LRP8/Dvl1 expression, increase destruction complex (Axin2/GSK3a/APC) expression, and promote degradation of β-catenin in colon carcinoma cell by inhibited NLRP3 expression.
Among these three compounds, the fluorosulfate derivative of Fulvestrant possesses significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER<sup>+</sup> breast cancer cell line MCF-7 and the fluorosulfate derivative of Combretastatin A4-a general anticancer drug currently being evaluated under clinical trials-exhibits a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29.
Implemented as a trackhub integrated to the University of California Santa Cruz (UCSC) genome browser, it can be easily added to any genome-wide annotation layer.To exemplify the trackhub usage we evaluate local DNA methylation boundaries, the aberrant DNA methylation of a CpG island located at the estrogen receptor 1 (ESR1) in breast and colon cancer, and the hypermethylation of the Homeobox HOXA gene cluster and the EN1 gene in multiple cancer types.
In contrast, E2 could exert protective effects in cancer cells by activating apoptosis when the ERβ level prevails on that of ERα as in colon cancer cell lines.
Thus upregulation of ER-β status by specific food-borne ER-ligands such as soy isoflavones could potentially be a dietary prevention or therapeutic strategy for colon cancer.
The tumor suppressor genes p15(INK)⁴(b) and p16(INK)⁴(a) as well as the estrogen receptor-α (ESR1) gene are abnormally methylated and expressed in colon cancer.
Protein tyrosine kinase and estrogen receptor-dependent pathways regulate the synthesis and distribution of glycosaminoglycans/proteoglycans produced by two human colon cancer cell lines.
In addition, some investigators have identified an age-related increase in DNA methylation of the ESR1 locus in the colon mucosa, suggesting that DNA methylation may be a pre-neoplastic change that increases the risk of colon adenomas and colon cancer.
The aim of this study was to determine the relative mRNA expression levels for ER subtypes and ERbeta isoforms in colon tumors, normal colonic mucosa, and colon cancer cell lines.