| First Author | Thiebaut C | Year | 2017 |
| Journal | PLoS One | Volume | 12 |
| Issue | 3 | Pages | e0173931 |
| PubMed ID | 28301550 | Mgi Jnum | J:246754 |
| Mgi Id | MGI:5917512 | Doi | 10.1371/journal.pone.0173931 |
| Citation | Thiebaut C, et al. (2017) Mammary epithelial cell phenotype disruption in vitro and in vivo through ERalpha36 overexpression. PLoS One 12(3):e0173931 |
| abstractText | Estrogen receptor alpha 36 (ERalpha36) is a variant of the canonical estrogen receptor alpha (ERalpha66), widely expressed in hormone sensitive cancer cells and whose high expression level correlates with a poor survival prognosis for breast cancer patients. While ERalpha36 activity have been related to breast cancer progression or acquired resistance to treatment, expression level and location of ERalpha36 are poorly documented in the normal mammary gland. Therefore, we explored the consequences of a ERalpha36 overexpression in vitro in MCF-10A normal mammary epithelial cells and in vivo in a unique model of MMTV-ERalpha36 transgenic mouse strain wherein ERalpha36 mRNA was specifically expressed in the mammary gland. By a combination of bioinformatics and computational analyses of microarray data, we identified hierarchical gene networks, downstream of ERalpha36 and modulated by the JAK2/STAT3 signaling pathway. Concomitantly, ERalpha36 overexpression lowered proliferation rate but enhanced migration potential and resistance to staurosporin-induced apoptosis of the MCF-10A cell line. In vivo, ERalpha36 expression led to duct epithelium thinning and disruption in adult but not in prepubescent mouse mammary gland. These phenotypes correlated with a loss of E-cadherin expression. Here, we show that an enhanced expression of ERalpha36 is sufficient, by itself, to disrupt normal breast epithelial phenotype in vivo and in vitro through a dominant-positive effect on nongenomic estrogen signaling pathways. These results also suggest that, in the presence of adult endogenous steroid levels, ERalpha36 overexpression in vivo contributes to alter mammary gland architecture which may support pre-neoplastic lesion and augment breast cancer risk. |
