Characterization of the oncogenic activity of the novel TRIM59 gene in mouse cancer models

Fatma Valiyeva, Fei Jiang, Ahmed Elmaadawi, Madeleine Moussa, Siu Pok Yee, Leda Raptis, Jonathan I. Izawa, Burton B. Yang, Norman M. Greenberg, Fen Wang, Jim W. Xuan

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

A novel TRIM family member, TRIM59 gene was characterized to be upregulated in SV40 Tag oncogene - directed transgenic and knockout mouse prostate cancer models as a signaling pathway effector. We identified two phosphorylated forms of TRIM59 (p53 and p55) and characterized them using purified TRIM59 proteins from mouse prostate cancer models at different stages with wild-type mice and NIH3T3 cells as controls. p53/p55-TRIM59 proteins possibly represent Ser/Thr and Tyr phosphorylation modifications, respectively. Quantitative measurements by ELISA showed that the p-Ser/Thr TRIM59 correlated with tumorigenesis, whereas the p-Tyr-TRIM59 protein correlated with advanced cancer of the prostate (CaP). The function of TRIM59 was elucidated using short hairpin RNA (shRNA)-mediated knockdown of the gene in human CaP cells, which caused S-phase cell-cycle arrest and cell growth retardation. A hit-and-run effect of TRIM59 shRNA knockdown was observed 24 hours posttransfection. Differential cDNA microarrray analysis was conducted, which showed that the initial and rapid knockdown occurred early in the Ras signaling pathway. To confirm the proto-oncogenic function of TRIM59 in the Ras signaling pathway, we generated a transgenic mouse model using a prostate tissue - specific gene (PSP94) to direct the upregulation of the TRIM59 gene. Restricted TRIM59 gene upregulation in the prostate revealed the full potential for inducing tumorigenesis, similar to the expression of SV40 Tag, and coincided with the upregulation of genes specific to the Ras signaling pathway and bridging genes for SV40 Tag - mediated oncogenesis. The finding of a possible novel oncogene in animal models will implicate a novel strategy for diagnosis, prognosis, and therapy for cancer.

Original languageEnglish (US)
Pages (from-to)1229-1240
Number of pages12
JournalMolecular Cancer Therapeutics
Volume10
Issue number7
DOIs
StatePublished - Jul 2011

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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