A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells

Yong Xu; Fang Fang; Gabriele Ludewig; Grace Jones; Davy Jones

doi:10.1089/1044549041474788

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A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells

Journal article

Peer reviewed

A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells

Yong Xu, Fang Fang, Gabriele Ludewig, Grace Jones and Davy Jones

DNA and cell biology, Vol.23(7), pp.419-429

07/2004

DOI: 10.1089/1044549041474788

PMID: 15294091

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Abstract

Survivin, a unique antiapoptotic factor, plays an important role in cell cycle regulation. Numerous clinical studies have shown that survivin is markedly overexpressed in most common types of cancer, suggesting that transcriptional deregulation is a major mechanism involved in aberrant expression of survivin in cancers. In this study, we have identified several polymorphisms in the survivin gene promoter. One of these polymorphisms is located at CDE/CHR repressor elements and appears to be a common mutation with high frequency among cancer cell lines compared to normal cell line controls. The presence of the mutation was correlated in these cell lines with increased survivin expression at the both mRNA and protein levels. Furthermore, gel mobility shift analysis and transcriptional analysis showed the mutation changed cell cycle-dependent transcription by modifying the binding motif of the CDE/CHR repressor. These results indicate that the high level of survivin in some cancers is, at least in part, due to a genetic defect in the promoter region of the human survivin gene, which causes derepression of survivin transcription apparently due to the mutated CDE/CHR repressor binding motifs.

Mutation

Cell Cycle - genetics

Promoter Regions, Genetic

Inhibitor of Apoptosis Proteins

Microtubule-Associated Proteins - genetics

Microtubule-Associated Proteins - metabolism

Humans

Gene Expression Regulation, Neoplastic

Molecular Sequence Data

Neoplasms - genetics

Base Sequence

Neoplasm Proteins

Transcription, Genetic

Tumor Cells, Cultured

Binding Sites

Details

Title: Subtitle: A mutation found in the promoter region of the human survivin gene is correlated to overexpression of survivin in cancer cells
Creators: Yong Xu - Molecular and Cellular Biology Section, Department of Biological Sciences, University of Kentucky, Lexington, USA. yxu0@uky.edu
Fang Fang
Gabriele Ludewig
Grace Jones
Davy Jones
Resource Type: Journal article
Publication Details: DNA and cell biology, Vol.23(7), pp.419-429
Publisher: United States
DOI: 10.1089/1044549041474788
PMID: 15294091
ISSN: 1044-5498
eISSN: 1557-7430
Grant note: CA081537 / NCI NIH HHS
Language: English
Date published: 07/2004
Academic Unit: Occupational and Environmental Health
Record Identifier: 9983997482202771

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