| First Author | Johnson AL | Year | 2015 |
| Journal | Oncotarget | Volume | 6 |
| Issue | 18 | Pages | 16304-20 |
| PubMed ID | 26008979 | Mgi Jnum | J:309332 |
| Mgi Id | MGI:6757385 | Doi | 10.18632/oncotarget.4059 |
| Citation | Johnson AL, et al. (2015) Vitamin D3-dependent VDR signaling delays ron-mediated breast tumorigenesis through suppression of beta-catenin activity. Oncotarget 6(18):16304-20 |
| abstractText | The Ron receptor is upregulated in human breast cancers and correlates with enhanced metastasis and reduced patient survival. Ron overexpression drives mammary tumorigenesis through direct beta-catenin activation and augmented tumor cell proliferation, migration and invasion. Ron and beta-catenin are also coordinately elevated in breast cancers. The vitamin D receptor (VDR) antagonizes beta-catenin signaling. Herein, we examined mammary tumor onset and progression using a Ron-driven murine model of breast tumorigenesis crossed with VDR deficient mice. VDR ablation accelerated mammary tumor onset and led to tumors that exhibited a desmoplastic phenotype and enhanced metastases. Tumor levels of active beta-catenin were markedly increased in the absence of VDR. In vitro, VDR activation in breast cancer cells reduced beta-catenin activation and transcriptional activity leading to elevated expression of the extracellular Wnt inhibitor dickkopf-related protein 1, and a reduction in the interaction of beta-catenin with the cyclin D1 promoter. Expression of a stabilized form or beta-catenin ablated the protective effects of VDR activation.Collectively, these studies delineate a protective role for VDR signaling in Ron-induced mammary tumorigenesis through disruption of beta-catenin activation. |
