title: Expression and the clinical significance of Wnt10a and Wnt10b in endometrial             cancer are associated with the Wnt/β-catenin pathway.
abstract: To determine the role played by the Wnt/β-catenin signaling pathway in the development of endometrial cancer (EC), we examined the expression of Wnt10a and Wnt10b in EC tissues and the correlation between their expression. Furthermore, the associations between these two proteins and the clinicopathological characteristics and prognosis of EC were also evaluated. In our search of alternative mechanisms, we investigated the impact of Wnt10b on proliferation and apoptosis of EC cells. Western blotting, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry were used to evaluate the expression of Wnt10b and some key proteins of the Wnt/β-catenin pathway, proliferation and apoptosis in EC. Our results showed that Wnt10b expression in EC tissues was significantly higher compared to that in hyperplastic and normal samples. The expression of Wnt10a in endometrioid cancer tissues was higher compared to that in other types of cancerous samples. The difference in Wnt10b levels was significant among subgroups for histological type, grade of differentiation, FIGO phase and lymphovascular metastasis. Furthermore, no correlation was observed between the expression of Wnt10a and Wnt10b. In the follow-up, Wnt10b gene expression was frequently upregulated in EC and associated with better prognostic clinicopathological markers in EC patients. Collectively, the in vitro data showed that the upregulated expression of Wnt10b in Ishikawa cells promoted proliferation and inhibited apoptosis through β-catenin and c-myc activation and adenomatous polyposis coli (APC) inhibition, which suggests that Wnt10b activates EC via the Wnt/β-catenin pathway. These results suggest that Wnt10b likely plays an important role in the development of EC. Furthermore, these results identify a role for Wnt10b in EC cells through promoting proliferation and inhibiting apoptosis, primarily through the activation of the Wnt/β-catenin pathway. The role played by Wnt10a in EC, however, still requires further investigation.
authors.affiliation: Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, Tianjin 300052, PR China.
authors.forename: Hongman
authors.initials: H
authors.lastname: Chen
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Wang
authors.forename: Fengxia
authors.initials: F
authors.lastname: Xue
mesh_terms: D025601:Adenomatous Polyposis Coli Protein / Q000378:metabolism; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology*; D004717:Endometrium / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D006801:Humans; D006965:Hyperplasia / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D018709:Statistics, Nonparametric; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: C555337:APC protein, human; D025601:Adenomatous Polyposis Coli Protein; C489427:MYC protein, human; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering; C484142:WNT10A protein, human; C491119:WNT10B protein, human; D051153:Wnt Proteins; D051176:beta Catenin