Authors
Salz, WhitneyEisenberg, Dan
Plescia, Janet
Garlick, David S.
Weiss, Robert M.
Wu, Xue-Ru
Sun, Tung-Tien
Altieri, Dario C.
UMass Chan Affiliations
Department of Cancer Biology and the Cancer CenterDocument Type
Journal ArticlePublication Date
2005-05-04Keywords
AnimalsButylhydroxybutylnitrosamine
Carcinogens
Disease Progression
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Humans
Membrane Proteins
Mice
Mice, Transgenic
Microtubule-Associated Proteins
Neoplasm Proteins
Polymerase Chain Reaction
Transgenes
Tumor Suppressor Protein p53
Urinary Bladder
Urinary Bladder Neoplasms
induced
Cancer Biology
Genetics
Urology
Metadata
Show full item recordAbstract
Gene signatures that predict aggressive tumor behavior at the earliest stages of disease, ideally before overt tissue abnormalities, are urgently needed. To search for such genes, we generated a transgenic model of survivin, an essential regulator of cell division and apoptosis overexpressed in cancer. Transgenic expression of survivin in the urinary bladder did not cause histologic abnormalities of the urothelium. However, microarray analysis revealed that survivin-expressing bladders exhibited profound changes in gene expression profile affecting extracellular matrix and inflammatory genes. Following exposure to a bladder carcinogen, N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBN), survivin transgenic animals exhibited accelerated tumor progression, preferential incidence of tumors as compared with premalignant lesions, and dramatically abbreviated survival. Conversely, transgenic expression of a survivin Thr34-->Ala dominant-negative mutant did not cause changes in gene expression or accelerated tumor progression after OH-BBN treatment. Therefore, survivin expression induces global transcriptional changes in the tissue microenvironment that may promote tumorigenesis. Detection of survivin or its associated gene signature may provide an early biomarker of aggressive tumor behavior before the appearance of tissue abnormalities.Source
Cancer Res. 2005 May 1;65(9):3531-4. Link to article on publisher's siteDOI
10.1158/0008-5472.CAN-04-4284Permanent Link to this Item
http://hdl.handle.net/20.500.14038/40725PubMed ID
15867343Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1158/0008-5472.CAN-04-4284