| First Author | Marzan CV | Year | 2011 |
| Journal | Dev Biol | Volume | 349 |
| Issue | 2 | Pages | 125-36 |
| PubMed ID | 20974122 | Mgi Jnum | J:168034 |
| Mgi Id | MGI:4881622 | Doi | 10.1016/j.ydbio.2010.10.018 |
| Citation | Marzan CV, et al. (2011) Adipocyte derived paracrine mediators of mammary ductal morphogenesis controlled by retinoic acid receptors. Dev Biol 349(2):125-36 |
| abstractText | We generated a transgenic (Tg)-mouse model expressing a dominant negative-(DN)-RARalpha, (RARalphaG303E) under adipocytes-specific promoter to explore the paracrine role of adipocyte retinoic acid receptors (RARs) in mammary morphogenesis. Transgenic adipocytes had reduced level of RARalpha, beta and gamma, which coincided with a severely underdeveloped pubertal and mature ductal tree with profoundly decreased epithelial cell proliferation. Transplantation experiments of mammary epithelium and of whole mammary glands implicated a fat-pad dependent paracrine mechanism in the stunted phenotype of the epithelial ductal tree. Co-cultures of primary adipocytes, or in vitro differentiated adipocyte cell line, with mammary epithelium showed that when activated, adipocyte-RARs contribute to generation of secreted proliferative and pro-migratory factors. Gene expression microarrays revealed a large number of genes regulated by adipocyte-RARs. Among them, pleiotrophin (PTN) was identified as the paracrine effectors of epithelial cell migration. Its expression was found to be strongly inhibited by DN-RARalpha, an inhibition relieved by pharmacological doses of all-trans retinoic acid (atRA) in culture and in vivo. Moreover, adipocyte-PTHR, another atRA responsive gene, was found to be an up-stream regulator of PTN. Overall, these results support the existence of a novel paracrine loop controlled by adipocyte-RAR that regulates the mammary ductal tree morphogenesis. |
