Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression of PTTG1 is associated with aggressive clear cell renal carcinoma

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Karl Dykema

PROVIDER: E-GEOD-25493 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Wondergem Bill B Zhang Zhongfa Z Huang Dachuan D Ong Choon Kiat CK Koeman Julie J Hof David Van't DV Petillo David D Ooi Aikseng A Anema John J Lane Brian B Kahnoski Richard J RJ Furge Kyle A KA Teh Bin Tean BT

Cancer research 20120717 17

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 amplific ...[more]

PMID: 22805307

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Project description: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. Here we show that PTTG1 is frequently amplified and overexpressed in clear cell renal cell carcinoma, the most common form of kidney cancer. 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 has to date remained a mystery, but is presumably the location of oncogenes that play an important role in ccRCC development or progression. The PTTG1 oncogene maps to chromosome 5q and shows frequent copy number gain in clear cell RCC, and is significantly overexpressed in tumor tissue relative to adjacent normal kidney. Furthermore, we have established a functional role for PTTG1 in ccRCC tumorigenesis and progression. PTTG1 ablation significantly 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 PTTG1 regulatory targets supports its role in the progression of localized ccRCC to invasive and metastatic disease, an idea further substantiated by PTTG1’s clinical correlation with high grade and high stage tumors and its association with poor prognosis. PTTG1-dependent overexpression of the Rho-GEF ECT2, another proto-oncogene, is observed in a number of ccRCC cell lines, and ECT2 overexpression correlates with PTTG1 overexpression, high stage, high grade, and poor prognosis in human ccRCC tumors. As GEF’s have been promoted as viable 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. SNP data on 74 ccRCC and 16 normal renal tissue samples were used to profile the cytogenetic gains or losses. The most frequent gains or losses were identified and gene expression data were then used to pinpoint the genes for further study.

Dataset Information

Expression of PTTG1 is associated with aggressive clear cell renal carcinoma

Publications

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

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