Please note that we have stopped the regular imports of Gene Expression Omnibus (GEO) data into ArrayExpress. This may not be the latest version of this experiment.
E-GEOD-25493 - Expression of PTTG1 is associated with aggressive clear cell renal carcinoma
Released on 31 July 2013, last updated on 5 August 2013
The pituitary tumor-transforming gene (PTTG1) is a recently discovered oncogene implicated in the malignant progression of a number of neoplasms. It has been shown to drive both endocrine and non-endocrine malignancies, but has not yet been studied in the context of renal cell carcinoma (RCC). Clear cell RCC (ccRCC) is cytogenetically characterized by deletion of chromosome 3p, harboring the von-Hippel Lindau tumor suppressor gene, and amplification of chromosome 5q. The significance of copy number gain of chromosome 5 is not clear, but is presumed to be the location of oncogenes that influence ccRCC development or progression. The PTTG1 oncogene maps to chromosome 5q, and here we show that PTTG1 is amplified in clear cell RCC, is overexpressed in tumor tissue relative to adjacent normal kidney, and expression is associated with high grade, high stage, and poor prognosis. Furthermore, we establish a functional role for PTTG1 in ccRCC tumorigenesis and progression. PTTG1 ablation reduces both the tumorigenic ability of ccRCC cells in vitro and in vivo and the invasive ability of these cells in vitro. An analysis of genes whose transcription is regulated by PTTG1 was supportive of an association with invasive and metastatic disease. PTTG1-dependent expression of the Rho-GEF ECT2, another proto-oncogene, is observed in a number of ccRCC cell lines, and ECT2 expression correlates with PTTG1 expression, high stage, high grade, and poor prognosis ccRCC. As GEF's have been promoted as potential drug targets for targeted cancer therapeutics, the relationship between the PTTG1 and ECT2 oncogenes may be able to be exploited for the treatment of this disease. PTTG1 was knocked down by siRNA.
transcription profiling by array
Expression of the PTTG1 oncogene is associated with aggressive clear cell renal cell carcinoma. Wondergem B, Zhang Z, Huang D, Ong CK, Koeman J, Hof DV, Petillo D, Ooi A, Anema J, Lane B, Kahnoski RJ, Furge KA, Teh BT. , PMID:22805307