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

Stephanie L. Easter, Elizabeth H. Mitchell, Sarah E. Baxley, Renee Desmond, Andra R. Frost, Rosa Serra

Research output: Contribution to journalArticle

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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 downregulated 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.

Original languageEnglish (US)
Article number0113247
JournalPLoS One
Volume9
Issue number11
DOIs
StatePublished - Nov 17 2014

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Tumors
Phenotype
phenotype
neoplasms
Catenins
Neoplasms
Tissue
breasts
Breast
Switches
genetically modified organisms
mice
Human Mammary Glands
mammary glands
cell culture
epithelial cells
Stem Cells
Down-Regulation
Cell Culture Techniques
Epithelial Cells

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Easter, S. L., Mitchell, E. H., Baxley, S. E., Desmond, R., Frost, A. R., & Serra, R. (2014). Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors. PLoS One, 9(11), [0113247]. https://doi.org/10.1371/journal.pone.0113247

Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors. / Easter, Stephanie L.; Mitchell, Elizabeth H.; Baxley, Sarah E.; Desmond, Renee; Frost, Andra R.; Serra, Rosa.

In: PLoS One, Vol. 9, No. 11, 0113247, 17.11.2014.

Research output: Contribution to journalArticle

Easter, SL, Mitchell, EH, Baxley, SE, Desmond, R, Frost, AR & Serra, R 2014, 'Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors', PLoS One, vol. 9, no. 11, 0113247. https://doi.org/10.1371/journal.pone.0113247
Easter SL, Mitchell EH, Baxley SE, Desmond R, Frost AR, Serra R. Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors. PLoS One. 2014 Nov 17;9(11). 0113247. https://doi.org/10.1371/journal.pone.0113247
Easter, Stephanie L. ; Mitchell, Elizabeth H. ; Baxley, Sarah E. ; Desmond, Renee ; Frost, Andra R. ; Serra, Rosa. / Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors. In: PLoS One. 2014 ; Vol. 9, No. 11.
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