콘텐츠로 건너뛰기
Merck
  • Wnt5a suppresses tumor formation and redirects tumor phenotype in MMTV-Wnt1 tumors.

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

PloS one (2014-11-18)
Stephanie L Easter, Elizabeth H Mitchell, Sarah E Baxley, Renee Desmond, Andra R Frost, Rosa Serra
초록

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.

MATERIALS
제품 번호
브랜드
제품 설명

Sigma-Aldrich
Anti-Active-β-Catenin (Anti-ABC) Antibody, clone 8E7, clone 8E7, Upstate®, from mouse
Sigma-Aldrich
Monoclonal Anti-KRT8 antibody produced in mouse, clone 3E3, purified immunoglobulin, buffered aqueous solution
Sigma-Aldrich
Hematoxylin, certified by the Biological Stain Commission
Sigma-Aldrich
Hematoxylin