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HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes.

ABSTRACT: The AT-hook transcription factor HMGA2 is an oncogene involved in the tumorigenesis of many malignant neoplasms. HMGA2 overexpression is common in both early and late-stage high-grade ovarian serous papillary carcinoma. To test whether HMGA2 participates in the initiation of ovarian cancer and promotion of aggressive tumor growth, we examined the oncogenic properties of HMGA2 in ovarian surface epithelial (OSE) cell lines. We found that introduction of HMGA2 overexpression was sufficient to induce OSE transformation in vitro. HMGA2-mediated OSE transformation resulted in tumor formation in the xenografts of nude mice. By silencing HMGA2 in HMGA2-overexpressing OSE and ovarian cancer cell lines, the aggressiveness of tumor cell growth behaviors was partially suppressed. Global gene profiling analyses revealed that HMGA2-mediated tumorigenesis was associated with expression changes of target genes and microRNAs that are involved in epithelial-to-mesenchymal transition (EMT). Lumican, a tumor suppressor that inhibits EMT, was found to be transcriptionally repressed by HMGA2 and was frequently lost in human high-grade serous papillary carcinoma. Our findings show that HMGA2 overexpression confers a powerful oncogenic signal in ovarian cancers through the modulation of EMT genes.

SUBMITTER: Wu J

PROVIDER: S-EPMC4434602 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes.

Wu Jingjing J Liu Zhaojian Z Shao Changshun C Gong Yaoqin Y Hernando Eva E Lee Peng P Narita Masashi M Muller William W Liu Jinsong J Wei Jian-Jun JJ

Cancer research 20110111 2

The AT-hook transcription factor HMGA2 is an oncogene involved in the tumorigenesis of many malignant neoplasms. HMGA2 overexpression is common in both early and late-stage high-grade ovarian serous papillary carcinoma. To test whether HMGA2 participates in the initiation of ovarian cancer and promotion of aggressive tumor growth, we examined the oncogenic properties of HMGA2 in ovarian surface epithelial (OSE) cell lines. We found that introduction of HMGA2 overexpression was sufficient to indu ...[more]

PMID: 21224353

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HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes.

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HMGA2 overexpression-induced ovarian surface epithelial transformation is mediated through regulation of EMT genes.

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