| First Author | Hasson RM | Year | 2014 |
| Journal | Carcinogenesis | Volume | 35 |
| Issue | 1 | Pages | 96-102 |
| PubMed ID | 24104551 | Mgi Jnum | J:206078 |
| Mgi Id | MGI:5547866 | Doi | 10.1093/carcin/bgt323 |
| Citation | Hasson RM, et al. (2014) Estrogen receptor alpha or beta loss in the colon of Min/+ mice promotes crypt expansion and impairs TGFbeta and HNF3beta signaling. Carcinogenesis 35(1):96-102 |
| abstractText | Adenomatous polyposis coli (APC)-regulated Wnt and transforming growth factor-beta (TGFbeta) signaling cooperate in the intestine to maintain normal enterocyte functions. Human clinical trials showed that estrogen [17beta-estradiol (E2)], the ligand of nuclear receptors estrogen receptor alpha (ERalpha) and ERbeta, inhibited colorectal cancer (CRC) in women. Consistent with this finding, we reported that E2, ERalpha and ERbeta suppressed intestinal tumorigenesis in the C57BL/6J-Min/+ (Min/+) mouse, a CRC model. Here, we extended our results with further comparisons of colon and small intestine from intact female Apc (+/+) (WT), Min/+ and ER-deficient Min/+ mice. In the colon of ER-deficient Min/+ mice, ER loss reduced TGFbeta signaling in crypt base cells as evidenced by minimal expression of the effectors Smad 2, 3 and 4 in these strains. We also found reduced expression of Indian hedgehog (Ihh), bone morphogenetic protein 4 and hepatocyte nuclear factor 3beta or FoxA2, factors needed for paracrine signaling between enterocytes and mesenchyme. In proximal colon, ER loss produced a >10-fold increased incidence of crypt fission, a marker for wound healing and tumor promotion. These data, combined with our previous work detailing the specific roles of E2, ERalpha and ERbeta in the colon, suggest that ER activity helps to maintain the intestinal stem cell (ISC) microenvironment by modulating epithelial-stromal crosstalk in ways that regulate cytokine, Wnt and Ihh availability in the extracellular matrix (ECM). |
