Department of Cancer Biology and the Cancer Center
Animals; Butylhydroxybutylnitrosamine; 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
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.
DOI of Published Version
Cancer Res. 2005 May 1;65(9):3531-4. Link to article on publisher's site
Salz, Whitney; Eisenberg, Dan; Plescia, Janet; Garlick, David S.; Weiss, Robert M.; Wu, Xue-Ru; Sun, Tung-Tien; and Altieri, Dario C., "A survivin gene signature predicts aggressive tumor behavior" (2005). Open Access Articles. 353.