TRIP-Br2 Promotes Oncogenesis in Nude Mice and is Frequently Overexpressed in Multiple Human Tumors

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TRIP-Br2 Promotes Oncogenesis in Nude Mice and is Frequently Overexpressed in Multiple Human Tumors

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Title: TRIP-Br2 Promotes Oncogenesis in Nude Mice and is Frequently Overexpressed in Multiple Human Tumors
Author: Cheong, Jit Kong; Gunaratnam, Lakshman; Zang, Zhi Jiang; Yang, Christopher M; Nasr, Susan L; Sim, Khe Guan; Peh, Bee Keow; Rashid, Suhaimi Bin Abdul; Salto-Tellez, Manuel; Hsu, Stephen I; Sun, Xiaoming; Bonventre, Joseph Vincent

Note: Order does not necessarily reflect citation order of authors.

Citation: Cheong, Jit Kong, Lakshman Gunaratnam, Zhi Jiang Zang, Christopher M. Yang, Xiaoming Sun, Susan L. Nasr, Khe Guan Sim, et al. 2009. TRIP-Br2 promotes oncogenesis in nude mice and is frequently overexpressed in multiple human tumors. Journal of Translational Medicine 7:8.
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Abstract: Background: Members of the TRIP-Br/SERTAD family of mammalian transcriptional coregulators have recently been implicated in E2F-mediated cell cycle progression and tumorigenesis. We, herein, focus on the detailed functional characterization of the least understood member of the TRIP-Br/SERTAD protein family, TRIP-Br2 (SERTAD2). Methods: Oncogenic potential of TRIP-Br2 was demonstrated by (1) inoculation of NIH3T3 fibroblasts, which were engineered to stably overexpress ectopic TRIP-Br2, into athymic nude mice for tumor induction and (2) comprehensive immunohistochemical high-throughput screening of TRIP-Br2 protein expression in multiple human tumor cell lines and human tumor tissue microarrays (TMAs). Clinicopathologic analysis was conducted to assess the potential of TRIP-Br2 as a novel prognostic marker of human cancer. RNA interference of TRIP-Br2 expression in HCT-116 colorectal carcinoma cells was performed to determine the potential of TRIP-Br2 as a novel chemotherapeutic drug target. Results: Overexpression of TRIP-Br2 is sufficient to transform murine fibroblasts and promotes tumorigenesis in nude mice. The transformed phenotype is characterized by deregulation of the E2F/DP-transcriptional pathway through upregulation of the key E2F-responsive genes CYCLIN E, CYCLIN A2, CDC6 and DHFR. TRIP-Br2 is frequently overexpressed in both cancer cell lines and multiple human tumors. Clinicopathologic correlation indicates that overexpression of TRIP-Br2 in hepatocellular carcinoma is associated with a worse clinical outcome by Kaplan-Meier survival analysis. Small interfering RNA-mediated (siRNA) knockdown of TRIP-Br2 was sufficient to inhibit cell-autonomous growth of HCT-116 cells in vitro. Conclusion: This study identifies TRIP-Br2 as a bona-fide protooncogene and supports the potential for TRIP-Br2 as a novel prognostic marker and a chemotherapeutic drug target in human cancer.
Published Version: doi://10.1186/1479-5876-7-8
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671481/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:5346780

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