Data from HMGA2 Participates in Transformation in Human Lung Cancer

<div>Abstract<p>Although previous studies have established a prominent role for <i>HMGA1</i> (formerly <i>HMG-I/Y</i>) in aggressive human cancers, the role of <i>HMGA2</i> (formerly <i>HMGI-C</i>) in malignant transformation has not been clearly defined. The <i>HMGA</i> gene family includes <i>HMGA1</i>, which encodes the HMGA1a and HMGA1b protein isoforms, and <i>HMGA2</i>, which encodes HMGA2. These chromatin-binding proteins function in transcriptional regulation and recent studies also suggest a role in cellular senescence. HMGA1 proteins also appear to participate in cell cycle regulation and malignant transformation, whereas HMGA2 has been implicated primarily in the pathogenesis of benign, mesenchymal tumors. Here, we show that overexpression of <i>HMGA2</i> leads to a transformed phenotype in cultured lung cells derived from normal tissue. Conversely, inhibiting <i>HMGA2</i> expression blocks the transformed phenotype in metastatic human non–small cell lung cancer cells. Moreover, we show that <i>HMGA2</i> mRNA and protein are overexpressed in primary human lung cancers compared with normal tissue or indolent tumors. In addition, there is a statistically significant correlation between HMGA2 protein staining by immunohistochemical analysis and tumor grade (<i>P</i> < 0.001). Our results indicate that <i>HMGA2</i> is an oncogene important in the pathogenesis of human lung cancer. Although additional studies with animal models are needed, these findings suggest that targeting HMGA2 could be therapeutically beneficial in lung cancer and other cancers characterized by increased <i>HMGA2</i> expression. (Mol Cancer Res 2008;6(5):743–50)</p></div>