Document Detail


PTEN loss and HOXA10 expression are associated with ovarian endometrioid adenocarcinoma differentiation and progression.
MedLine Citation:
PMID:  23276799     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Epithelial ovarian cancer is a heterogeneous disease that is subdivided into five major histotypes but the mechanisms driving their differentiation are not clear. Mutations in adenomatous polyposis coli (APC) and β-catenin are commonly observed in the human ovarian endometrioid adenocarcinoma (OEA) patients. However, the mechanisms subsequent to APC deletion in ovarian tumorigenesis have not been well characterized. We have conditionally deleted APC in the murine ovarian surface epithelium (OSE) and showed that its loss leads to development of epithelial inclusion cysts. High-grade OEAs with tightly packed villoglandular histology were observed in older APC-deleted mice. Phosphatase and tensin homolog (PTEN) expression was elevated in the early lesions but lost after progression to the more advanced tumors. Knockdown of APC or expression of a gain-of-function β-catenin similarly induced human OSE cells to develop tumors with endometrioid histology in xenografts. Expression of HOXA10 was induced in both the advanced APC-deleted murine tumors and in the tumor xenografts of human OSE cells with knocked-down APC. These results show that reduced APC activity is sufficient to induce formation of epithelial inclusion cysts and support OEA development and suggest that induced HOXA10 expression and loss of PTEN are key mechanisms driving endometrioid histotype differentiation and progression.
Authors:
Pradeep S Tanwar; Tomoko Kaneko-Tarui; Ho-Joon Lee; Lihua Zhang; Jose M Teixeira
Related Documents :
17186289 - Assessment of cd4+ t cells specific for the tumor antigen ssx-1 in cancer-free individu...
1382849 - Expression of tumor-associated epitopes on epstein-barr virus-immortalized b-cells and ...
23276799 - Pten loss and hoxa10 expression are associated with ovarian endometrioid adenocarcinoma...
15687709 - Glycoprotein tumor antigens for immunotherapy of breast cancer.
18413769 - Loss of ctl function among high-avidity tumor-specific cd8+ t cells following tumor inf...
12014649 - T-cell immunotherapy for human mk-1-expressing tumors using a fusion protein of the sup...
24480809 - Mir-656 inhibits glioma tumorigenesis through repression of bmpr1a.
16936589 - Case report. granular cell tumors of extremities: comparison of benign and malignant va...
21310649 - The frequent co-expression of the oncogenes pik3ca and pak1 in oral carcinomas.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-31
Journal Detail:
Title:  Carcinogenesis     Volume:  34     ISSN:  1460-2180     ISO Abbreviation:  Carcinogenesis     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-06-17     Revised Date:  2014-04-01    
Medline Journal Info:
Nlm Unique ID:  8008055     Medline TA:  Carcinogenesis     Country:  England    
Other Details:
Languages:  eng     Pagination:  893-901     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / genetics
Adenomatous Polyposis Coli / genetics*
Animals
Carcinoma, Endometrioid / genetics*,  metabolism,  pathology*
Cell Differentiation
Cell Transformation, Neoplastic / genetics
Disease Progression
Female
Homeodomain Proteins / genetics*
Humans
Mice
Mice, Knockout
Neoplasm Transplantation
Neoplasms, Glandular and Epithelial / genetics*,  pathology
Ovarian Neoplasms / genetics*,  pathology
Ovary / pathology
PTEN Phosphohydrolase / genetics*
Transplantation, Heterologous
Tumor Cells, Cultured
Wnt Signaling Pathway / genetics
beta Catenin / genetics
Grant Support
ID/Acronym/Agency:
HD052701/HD/NICHD NIH HHS; R01 HD052701/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Homeodomain Proteins; 0/beta Catenin; 164384-16-1/Hoxa10 protein, mouse; EC 3.1.3.48/Pten protein, mouse; EC 3.1.3.67/PTEN Phosphohydrolase
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Estrogen metabolism within the lung and its modulation by tobacco smoke.
Next Document:  Eicosapentaenoic acid (EPA) induces peroxisome proliferator-activated receptors and ameliorates expe...