| First Author | Easter SL | Year | 2014 |
| Journal | PLoS One | Volume | 9 |
| Issue | 11 | Pages | e113247 |
| PubMed ID | 25401739 | Mgi Jnum | J:225135 |
| Mgi Id | MGI:5691618 | Doi | 10.1371/journal.pone.0113247 |
| Citation | Easter SL, et al. (2014) Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors. PLoS One 9(11):e113247 |
| abstractText | Wnt5a is a non-canonical signaling Wnt that has been implicated in tumor suppression. We previously showed that loss of Wnt5a in MMTV-PyVmT tumors resulted in a switch in tumor phenotype resulting in tumors with increased basal phenotype and high Wnt/beta-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/beta-catenin signaling. To this end, we characterized tumor and non-tumor mammary tissue from MMTV-Wnt1 and double transgenic MMTV-Wnt1;MMTV-Wnt5a mice. Wnt5a containing mice demonstrated fewer tumors with increased latency when compared to MMTV-Wnt1 controls. Expression of markers for basal-like tumors was down-regulated in the tumors that formed in the presence of Wnt5a indicating a phenotypic switch. Reduced canonical Wnt signaling was detected in double transgenic tumors as a decrease in active beta-catenin protein and a decrease in Axin2 mRNA transcript levels. In non-tumor tissues, over-expression of Wnt5a in MMTV-Wnt1 mammary glands resulted in attenuation of phenotypes normally observed in MMTV-Wnt1 glands including hyperbranching and increased progenitor and basal cell populations. Even though Wnt5a could antagonize Wnt/beta-catenin signaling in primary mammary epithelial cells in culture, reduced Wnt/beta-catenin signaling was not detected in non-tumor MMTV-Wnt1;Wnt5a tissue in vivo. The data demonstrate that Wnt5a suppresses tumor formation and promotes a phenotypic shift in MMTV-Wnt1 tumors. |
