title: HMGA2 participates in transformation in human lung cancer.
abstract: Although previous studies have established a prominent role for HMGA1 (formerly HMG-I/Y) in aggressive human cancers, the role of HMGA2 (formerly HMGI-C) in malignant transformation has not been clearly defined. The HMGA gene family includes HMGA1, which encodes the HMGA1a and HMGA1b protein isoforms, and HMGA2, 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 HMGA2 leads to a transformed phenotype in cultured lung cells derived from normal tissue. Conversely, inhibiting HMGA2 expression blocks the transformed phenotype in metastatic human non-small cell lung cancer cells. Moreover, we show that HMGA2 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 (P < 0.001). Our results indicate that HMGA2 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 HMGA2 expression.
authors.affiliation: Hematology Division, the Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Francescopaolo
authors.initials: F
authors.lastname: Di Cello
authors.forename: Joelle
authors.initials: J
authors.lastname: Hillion
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hristov
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: Wood
authors.forename: Mita
authors.initials: M
authors.lastname: Mukherjee
authors.forename: Andrew
authors.initials: A
authors.lastname: Schuldenfrei
authors.forename: Jeanne
authors.initials: J
authors.lastname: Kowalski
authors.forename: Raka
authors.initials: R
authors.lastname: Bhattacharya
authors.forename: Raheela
authors.initials: R
authors.lastname: Ashfaq
authors.forename: Linda M S
authors.initials: LM
authors.lastname: Resar
mesh_terms: D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D002843:Chromatin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D025743:HMGA2 Protein / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D025743:HMGA2 Protein; D012333:RNA, Messenger