Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously identified and characterized a novel p53-regulated gene in mouse prostate cancer cells that was homologous to a human gene that had been identified in brain cancers and termed RTVP-1 or GLIPR. In this report, we document that the human RTVP-1 gene is also regulated by p53 and induces apoptosis in human prostate cancer cell lines. We show that the expression of the human RTVP-1 gene is down-regulated in human prostate cancer specimens compared with normal human prostate tissue at the mRNA and protein levels. We further document epigenetic changes consistent with RTVP-1 being a tumor suppressor in human prostate cancer.
 ...
PMID:RTVP-1, a tumor suppressor inactivated by methylation in prostate cancer. 1487 27

Wilms tumors (WTs) have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI) and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI) tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1) gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5'-region in WTs relative to normal tissue is observed in 21/24 (87.5%) of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%), with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK) control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs), supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs.
 ...
PMID:Hypomethylation and aberrant expression of the glioma pathogenesis-related 1 gene in Wilms tumors. 1803 Mar 65

After glioma pathogenesis-related protein 1 (GLIPR1/Glipr1) was identified, the expression of GLIPR1 was shown to be down-regulated in human prostate cancer, owing in part to methylation in the regulatory region of this gene in prostate cancer cells. Additional studies showed that GLIPR1/Glipr1 expression is induced by DNA-damaging agents independent of p53. Functional analysis of GLIPR1 using in vitro and in vivo gene-transfer approaches revealed both growth suppression and proapoptotic activities for mouse Glipr1 and human GLIPR1 in multiple cancer cell lines. The proapoptotic activities were dependent on production of reactive oxygen species and sustained c-Jun-NH(2) kinase signaling. It was interesting that adenoviral vector-mediated Glipr1 (AdGlipr1) transduction into prostate cancer tissues using an immunocompetent orthotopic mouse model revealed additional biologic activities consistent with tumor-suppressor functions. Significantly reduced tumor-associated angiogenesis and direct suppression of endothelial-cell sprouting activities were documented. In addition, AdGlipr1 strongly stimulated antitumor immune responses that resulted in specific cytotoxic T-lymphocyte activities in this model. Glipr1-related antitumor immunostimulatory activities were confirmed and extended in subsequent studies. Administration of a novel Glipr1 genemodified tumor cell vaccine had significant antitumor activity in a mouse model of recurrent prostate cancer. In conclusion, restoration of GLIPR1 function in prostate cancer cells through GLIPR1 gene-based or GLIPR protein-based delivery methods may provide a safe and effective approach for targeted therapy for a range of malignancies.
 ...
PMID:Glioma pathogenesis-related protein 1: tumor-suppressor activities and therapeutic potential. 2049 10