HMGA2 participates in transformation in human lung cancer

Francescopaolo Di Cello, Joelle Hillion, Alexandra Hristov, Lisa J. Wood, Mita Mukherjee, Andrew Schuldenfrei, Jeanne Kowalski, Raka Bhattacharya, Raheela Ashfaq, Linda M Smith Resar

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)743-750
Number of pages8
JournalMolecular Cancer Research
Volume6
Issue number5
DOIs
StatePublished - May 1 2008

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Lung Neoplasms
HMGA2 Protein
Neoplasms
HMGA1b Protein
HMGA Proteins
HMGA1a Protein
Phenotype
Cell Aging
Oncogenes
Non-Small Cell Lung Carcinoma
Chromatin
Cultured Cells
Cell Cycle
Carrier Proteins
Protein Isoforms
Animal Models
Staining and Labeling
Lung
Messenger RNA
Genes

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Di Cello, F., Hillion, J., Hristov, A., Wood, L. J., Mukherjee, M., Schuldenfrei, A., ... Smith Resar, L. M. (2008). HMGA2 participates in transformation in human lung cancer. Molecular Cancer Research, 6(5), 743-750. https://doi.org/10.1158/1541-7786.MCR-07-0095

HMGA2 participates in transformation in human lung cancer. / Di Cello, Francescopaolo; Hillion, Joelle; Hristov, Alexandra; Wood, Lisa J.; Mukherjee, Mita; Schuldenfrei, Andrew; Kowalski, Jeanne; Bhattacharya, Raka; Ashfaq, Raheela; Smith Resar, Linda M.

In: Molecular Cancer Research, Vol. 6, No. 5, 01.05.2008, p. 743-750.

Research output: Contribution to journalArticle

Di Cello, F, Hillion, J, Hristov, A, Wood, LJ, Mukherjee, M, Schuldenfrei, A, Kowalski, J, Bhattacharya, R, Ashfaq, R & Smith Resar, LM 2008, 'HMGA2 participates in transformation in human lung cancer', Molecular Cancer Research, vol. 6, no. 5, pp. 743-750. https://doi.org/10.1158/1541-7786.MCR-07-0095
Di Cello F, Hillion J, Hristov A, Wood LJ, Mukherjee M, Schuldenfrei A et al. HMGA2 participates in transformation in human lung cancer. Molecular Cancer Research. 2008 May 1;6(5):743-750. https://doi.org/10.1158/1541-7786.MCR-07-0095
Di Cello, Francescopaolo ; Hillion, Joelle ; Hristov, Alexandra ; Wood, Lisa J. ; Mukherjee, Mita ; Schuldenfrei, Andrew ; Kowalski, Jeanne ; Bhattacharya, Raka ; Ashfaq, Raheela ; Smith Resar, Linda M. / HMGA2 participates in transformation in human lung cancer. In: Molecular Cancer Research. 2008 ; Vol. 6, No. 5. pp. 743-750.
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