Wnt/[beta]-Catenin Signaling Pathway Upregulates c-Myc Expression to Promote Cell Proliferation of P19 Teratocarcinoma Cells

• Published in: Anatomical record (Hoboken, N.J. : 2007) Vol. 295; no. 12; p. 2104
• Main Authors: Zhang, Shuai, Li, Yi, Wu, Yuling, Shi, Kun, Bing, Lujun, Hao, Jing
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc 01-12-2012
• ISSN: 1932-8486; 1932-8494
• DOI: 10.1002/ar.22592

Aberrant activation of the Wnt/[beta]-catenin signaling pathway is a common event in human tumor progression. Wnt signaling has also been implicated in maintaining a variety of adult and embryonic stem cells by imposing a restraint to differentiation. To understand the function and mechanism of Wnt/[beta]-catenin signaling on the pathogenesis of teratocarcinoma, we used the mouse teratocarcinoma P19 cell line as a model in vitro. Gsk3[beta] specific inhibitor (SB216763) was used to activate Wnt/[beta]-catenin signaling. All trans-retinoic acid (RA) was used to induce P19 cell differentiation. At different culture times, gene expression was examined by immunofluorescence staining, quantitative real-time PCR, and Western-blotting; BrdU incorporation assays were performed to measure P19 cell proliferation. Small interference RNA technology was used to downregulate c-myc expression. The results showed that SB216763 induced the nuclear translocation of [beta]-catenin, upregulated the expression of c-myc and pluripotency related genes, oct4, sox2 and nanog, and blocked cell differentiation induced by all trans-RA. The proliferation of P19 cells was significantly enhanced by SB216763, as well as c-myc overexpression. C-myc downregulation inhibited P19 cell proliferation caused by activation of Wnt/[beta]-catenin signaling and induced P19 cell differentiation. In conclusion, activation of the Wnt/[beta]-catenin pathway could promote the proliferation and inhibit the differentiation of mouse teratocarcinoma cells by upregulation of c-myc expression. Anat Rec, 2012. © 2012 Wiley Periodicals, Inc.