Expression of the PTTG1 oncogene is associated with aggressive clear cell renal cell carcinoma

Bill Wondergem, Zhongfa Zhang, Dachuan Huang, Choon Kiat Ong, Julie Koeman, David Van t. Hof, David Petillo, Aikseng Ooi, John Anema, Brian Lane, Richard J. Kahnoski, Kyle A. Furge, Bin Tean Teh

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The pituitary tumor transforming gene (PTTG1) is a recently discovered oncogene implicated in malignant progression of both endocrine and nonendocrine malignancies. Clear cell renal cell carcinoma (ccRCC) is cytogenetically characterized by chromosome 3p deletions that harbor the ccRCC-related von Hippel-Lindau, PBRM1, BAP1, and SETD2 tumor suppressor genes, along with chromosome 5q amplifications where the significance has been unclear. PTTG1 localizes to the chromosome 5q region where amplifications occur in ccRCC. In this study, we report a functional role for PTTG1 in ccRCC tumorigenesis. PTTG1 was amplified in ccRCC, overexpressed in tumor tissue, and associated with high-grade tumor cells and poor patient prognosis. In preclinical models, PTTG1 ablation reduced tumorigenesis and invasion. An analysis of gene expression affected by PTTG1 indicated an association with invasive and metastatic disease. PTTG1-dependent expression of the RhoGEF proto-oncogene ECT2 was observed in a number of ccRCC cell lines. Moreover, ECT2 expression correlated with PTTG1 expression and poor clinical features. Together, our findings reveal features of PTTG1 that are consistent with its identification of an oncogene amplified on chromsome 5q in ccRCC, where it may offer a novel therapeutic target of pathologic significance in this disease.

Original languageEnglish (US)
Pages (from-to)4361-4371
Number of pages11
JournalCancer Research
Volume72
Issue number17
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Wondergem, B., Zhang, Z., Huang, D., Ong, C. K., Koeman, J., Hof, D. V. T., Petillo, D., Ooi, A., Anema, J., Lane, B., Kahnoski, R. J., Furge, K. A., & Teh, B. T. (2012). Expression of the PTTG1 oncogene is associated with aggressive clear cell renal cell carcinoma. Cancer Research, 72(17), 4361-4371. https://doi.org/10.1158/0008-5472.CAN-11-2330