Anti-PYGO2 (full length) polyclonal antibody

This study was undertaken to define whether differences in the expression of Wnt pathway components are present between normal colonic mucosa, early (tubular) adenomas and villous adenomas which have a higher malignant potential. Normal mucosa, tubular adenomas and villous adenomas were obtained from twelve patients. RNA was isolated and utilized for Wnt pathway-specific membrane array expression analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescent immunohistochemistry (IHC) were utilized for confirmatory analyses. Fifteen Wnt pathway-related genes showed differential expression between villous adenomas and normal mucosa and villous and tubular adenomas at a significance level of p<0.01. Genes involved in canonical Wnt (B-catenin) signaling with increased expression in villous adenomas included wnt1, fz2, csnk2A2, pygo2, pygo1, frat2 and myc, the latter confirmed by qRT-PCR and IHC. Myc protein expression was confined primarily to stromal components of villous adenomas. Genes involved in non-canonical Wnt signaling with increased expression in villous adenomas included rho-u, daam1, damm2, cxxc4 and nlk. Successive increases in the expression of ctnnb1 (B-catenin) from normal to tubular adenomas to villous adenomas was seen. The Wnt pathway gene expression profile can differentiate between tubular and villous adenomas. These data suggest that Wnt signaling regulation changes during the progression from normal mucosa to tubular adenomas to villous adenomas. Expression of Myc in adenoma stroma suggests a dynamic signaling network within adenomas between mucosal and stromal elements. Inhibition of the Wnt pathway may provide a novel approach for cancer prevention in patients with benign tubular adenomas.

Understanding the epigenetic mechanisms that control the activation of adult stem cells holds the promise of tissue and organ regeneration. Hair follicle stem cells have emerged as a prime model to study stem cell activation. Wnt/beta-catenin signaling controls multiple aspects of skin epithelial regeneration, with its excessive activity promoting the hyperactivation of hair follicle stem/progenitor cells and tumorigenesis. The contribution of chromatin factors in regulating Wnt/beta-catenin pathway function in these processes is unknown. Here, we show that chromatin effector Pygopus homolog 2 (Pygo2) produced by the epithelial cells facilitates depilation-induced hair regeneration, as well as beta-catenin-induced activation of hair follicle stem/early progenitor cells and trichofolliculoma-like skin hyperplasia. Pygo2 maximizes the expression of Wnt/beta-catenin targets, but is dispensable for beta-catenin-mediated expansion of LIM/homeobox protein Lhx2(+) cells, in the stem/early progenitor cell compartment of the hair follicle. Moreover, beta-catenin and Pygo2 converge to induce the accumulation and acetylation of tumor suppressor protein p53 upon the cell cycle entry of hair follicle early progenitor cells and in cultured keratinocytes. These findings identify Pygo2 as an important regulator of Wnt/beta-catenin function in skin epithelia and p53 activation as a prominent downstream event of beta-catenin/Pygo2 action in stem cell activation.