Wnt5a Suppresses Tumor Formation and Redirects Tumor Phenotype in MMTV-Wnt1 Tumors

Autor: Rosa Serra, Sarah E. Baxley, Andra R. Frost, Elizabeth H. Mitchell, Stephanie L. Easter, Renee A. Desmond
Rok vydání: 2014
Předmět:
Male
Pathology
Organogenesis
Fluorescent Antibody Technique
lcsh:Medicine
Mammary Gland Development
Immunoenzyme Techniques
Mice
0302 clinical medicine
Cell Signaling
Breast Tumors
Medicine and Health Sciences
WNT1
lcsh:Science
Cells
Cultured
beta Catenin
0303 health sciences
Multidisciplinary
Reverse Transcriptase Polymerase Chain Reaction
Wnt signaling pathway
Beta-Catenin Signaling
Phenotype
WNT5A
Oncology
030220 oncology & carcinogenesis
embryonic structures
Female
Stem cell
Research Article
Signal Transduction
medicine.medical_specialty
animal structures
Transgene
Blotting
Western
Mice
Transgenic
Wnt1 Protein
Biology
Real-Time Polymerase Chain Reaction
Wnt-5a Protein
03 medical and health sciences
Mammary Glands
Animal
Breast Cancer
AXIN2
medicine
Animals
RNA
Messenger
030304 developmental biology
lcsh:R
Mammary Neoplasms
Experimental
Biology and Life Sciences
Cancers and Neoplasms
Epithelial Cells
Cell Biology
Gland Development
Mice
Inbred C57BL
Wnt Proteins
body regions
Mammary Tumor Virus
Mouse
Cancer research
lcsh:Q
sense organs
Organism Development
Immunostaining
Developmental Biology
Zdroj: PLoS ONE, Vol 9, Iss 11, p e113247 (2014)
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0113247
Popis: 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.
Databáze: OpenAIRE
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