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Am J Cancer Res. 2016 Jan 15;6(2):249-59. eCollection 2016.

Overexpression and oncogenic function of HMGA2 in endometrial serous carcinogenesis.

Author information

1
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University Jinan, Shandong, China.
2
Department of Molecular and Cellular Biology, University of Arizona Tucson, Arizona, USA.
3
Department of Cell Biology, Shandong University School of Medicine Jinan, Shandong, China.
4
Department of Obstetrics and Gynecology, Qilu Hospital, Shandong UniversityJinan, Shandong, China; Department of Pathology, University of Arizona College of MedicineAZ, USA; Department of Pathology, University of Texas Southwestern Medical CenterDallas, TX, USA; Department of Obstetrics and Gynecology, University of Texas Southwestern Medical CenterDallas, TX, USA.

Abstract

The high-mobility group A protein 2 (HMGA2) is a non-histone chromatin factor highly expressed in fetal tissue and malignant tumors but rarely detected within normal adult tissues. The clinical implications and biological functions of HMGA2 in endometrial carcinoma are largely unknown. Here we report that HMGA2 expression was barely detected in benign endometrium samples (2 of 28 samples). However, HMGA2 expression increased significantly from precancerous lesion endometrial glandular dysplasia (7 of 17, 41.2%), to serous endometrial intraepithelial carcinoma (5 of 8, 62.5%) and to full blown endometrial serous carcinoma (39 of 59, 66.1%). Functional characterization of HMGA2 revealed that the gene has both tumor growth promotion and metastasis. In addition, HMGA2 induced epithelial-mesenchymal transition (EMT) through modulation vimentin and β-catenin. Furthermore, HMGA2 overexpression started from endometrial serous precancers, non-invasive cancers, as well as in full blown carcinomas in a p53 knockout mouse model we recently established in our laboratory. Our findings suggest that HMGA2 may serve as a useful diagnostic marker in the assessment of endometrial serous cancer and its precursor lesions.

KEYWORDS:

EMT; HMGA2; endometrial serous carcinoma; metastasis; tumor growth

PMID:
27186400
PMCID:
PMC4859657

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