| First Author | Paatero I | Year | 2014 |
| Journal | J Biol Chem | Volume | 289 |
| Issue | 32 | Pages | 22459-69 |
| PubMed ID | 24966332 | Mgi Jnum | J:216619 |
| Mgi Id | MGI:5609103 | Doi | 10.1074/jbc.M113.533497 |
| Citation | Paatero I, et al. (2014) Hypoxia-inducible factor-1alpha induces ErbB4 signaling in the differentiating mammary gland. J Biol Chem 289(32):22459-69 |
| abstractText | Conditional knock-out of Hif1a in the mouse mammary gland impairs lobuloalveolar differentiation during lactation. Here, we demonstrate that expression of ErbB4 was reduced in the lobulalveoli of mice with mammary gland-specific deletion of Hif1a. Erbb4 was not, however, a direct target gene for transcriptional regulation by HIF-1alpha in vitro. HIF-1alpha overexpression or HIF accumulating prolyl hydroxylase inhibitors reduced ErbB4 endocytosis, promoted transcriptional co-regulatory activity of ErbB4, and stimulated ErbB4-induced differentiation of mammary carcinoma cells. Consistently, RNA interference-mediated down-regulation of HIF-1alpha resulted in reduced ErbB4 protein amount and reduced mammary carcinoma cell differentiation. These findings indicate that HIF-1alpha is a physiologically relevant regulator of ErbB4 and that ErbB4 is involved in HIF-regulated differentiation of the mammary gland. |
