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Title: Expression of PTTG1 is associated with aggressive clear cell RCC      
dateReleased:
12-31-2010
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.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-25399
refinement:
raw
alternateIdentifiers:
25399
keywords:
functional genomics
availability:
available
types:
gene expression
name:
Homo sapiens
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-25399/E-GEOD-25399.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-25399/E-GEOD-25399.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE25399
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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