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Journal article
STAT5A/B Gene Locus Undergoes Amplification during Human Prostate Cancer Progression
The American journal of pathology, v 182(6), pp 2264-2275
01 Jun 2013
PMID: 23660011
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The molecular mechanisms underlying progression of prostate cancer (PCa) to castrate-resistant (CR) and metastatic disease are poorly understood. Our previous mechanistic work shows that inhibition of transcription factor Stat5 by multiple alternative methods induces extensive rapid apoptotic death of Stat5-positive PCa cells in vitro and inhibits PCa xenograft tumor growth in nude mice. Furthermore, STAT5A/B induces invasive behavior of PCa cells in vitro and in vivo, suggesting involvement of STAT5A/B in PCa progression. Nuclear STAT5A/B protein levels are increased in high-grade PCas, CR PCas, and distant metastases, and high nuclear STAT5A/B expression predicts early disease recurrence and PCa-specific death in clinical PCas. Based on these findings, STAT5A/B represents a therapeutic target protein for advanced PCa. The mechanisms underlying increased Stat5 protein levels in PCa are unclear. Herein, we demonstrate amplification at the STAT5A/B gene locus in a significant fraction of clinical PCa specimens. STAT5A/B gene amplification was more frequently found in PCas of high histologic grades and in CR distant metastases. Quantitative in situ analysis revealed that STAT5A/B gene amplification was associated with increased STAT5A/B protein expression in PCa. Functional studies showed that increased STAT5A/B copy numbers conferred growth advantage in PCa cells in vitro and as xenograft tumors in vivo. The work presented herein provides the first evidence of somatic STAT5A/B gene amplification in clinical PCas.
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Details
- Title
- STAT5A/B Gene Locus Undergoes Amplification during Human Prostate Cancer Progression
- Creators
- Bassem R. Haddad - Georgetown UniversityLei Gu - Kimmel Cancer CenterTuomas Mirtti - University of HelsinkiAyush Dagvadorj - Kimmel Cancer CenterParaskevi Vogiatzi - Kimmel Cancer CenterDavid T. Hoang - Kimmel Cancer CenterRenu Bajaj - Thomas Jefferson UniversityBenjamin Leiby - Thomas Jefferson UniversityElyse Ellsworth - Kimmel Cancer CenterShauna Blackmon - Kimmel Cancer CenterChristian Ruiz - Basel Institute for ImmunologyMark Curtis - Thomas Jefferson UniversityPaolo Fortina - Kimmel Cancer CenterAdam Ertel - Sidney Kimmel Cancer CenterChengbao Liu - Kimmel Cancer CenterHallgeir Rui - Thomas Jefferson UniversityTapio Visakorpi - Thomas Jefferson UniversityLukas Bubendorf - Basel Institute for ImmunologyCostas D. Lallas - University of TampereEdouard J. Trabulsi - University of TamperePeter McCue - Thomas Jefferson UniversityLeonard Gomella - University of TampereMarja T. Nevalainen - Thomas Jefferson University
- Publication Details
- The American journal of pathology, v 182(6), pp 2264-2275
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- 135655 / Academy of Finland CA56036-08 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R21CA178755 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) 1RO1CA113580-01A1 / NIH National Cancer Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics; School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000319781800030
- Scopus ID
- 2-s2.0-84878221509
- Other Identifier
- 991019176803904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Pathology