Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors.

Academic Article

Abstract

  • 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/β-catenin signaling. The object of this study was to test the hypothesis that Wnt5a can act to inhibit tumors formed by activation of Wnt/β-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 β-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/β-catenin signaling in primary mammary epithelial cells in culture, reduced Wnt/β-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.
  • Published In

  • PLoS ONE  Journal
  • Keywords

  • Animals, Blotting, Western, Cells, Cultured, Epithelial Cells, Female, Fluorescent Antibody Technique, Immunoenzyme Techniques, Male, Mammary Glands, Animal, Mammary Neoplasms, Experimental, Mammary Tumor Virus, Mouse, Mice, Mice, Inbred C57BL, Mice, Transgenic, Phenotype, RNA, Messenger, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Wnt Proteins, Wnt-5a Protein, Wnt1 Protein, beta Catenin
  • Digital Object Identifier (doi)

    Authorlist

  • Easter SL; Mitchell EH; Baxley SE; Desmond R; Frost AR; Serra R
  • Start Page

  • e113247
  • Volume

  • 9
  • Issue

  • 11