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

Previously, we have demonstrated that GBX genes, a homeobox-containing human family of DNA-binding transcription factors consisting of GBX1 and GBX2, are overexpressed in a panel of human prostatic cancer cell lines (ie., TSU-pr1, PC3, DU145, and LNCaP) compared to normal prostate. In the present studies, specific primer sets were designed for reverse transcription-PCR detection of the expression of GBX1 versus GBX2 in human prostate cancer. These studies demonstrated that the GBX2 gene, but not the GBX1 gene, is consistently overexpressed in this panel of human prostate cancer cell lines compared to normal human prostate. Using a quantitative-competitive PCR analysis, GBX2 mRNA was expressed as 3 x 10(3) copies/microg RNA in normal prostate tissue and 4 x 10(4) copies/microg RNA in the immortalized normal neonatal prostate epithelial cell line 267B-1, as compared to 6 x 10(5), 5 x 10(5), 3 x 10(5), and 1 x 10(5) copies/microg RNA in TSU-pr1, DU145, LNCaP, and PC3 prostate cancer cell lines, respectively. To examine the importance of GBX2 expression for prostate cancer malignancy, GBX2-overexpressing TSU-pr1 and PC3 human prostatic cancer cells were transfected with a eukaryotic expression vector containing an antisense GBX2 homeobox domain cDNA. Stable transfectant clones with 5-10-fold decreased levels of GBX2 mRNA expression were obtained. When tested in vitro, the clonogenic ability of the GBX2 antisense transfectants was reduced by approximately 50% in both cell lines. When implanted s.c. into nude mice, the tumorigenicity of the antisense GBX2 transfectants from both human prostatic cancer cell lines was inhibited by more than 70% compared to the parental cells. These results suggest that expression of GBX2 gene is required for malignant growth of human prostate cells.
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PMID:Down-regulation of homeobox gene GBX2 expression inhibits human prostate cancer clonogenic ability and tumorigenicity. 953 37

Previous studies demonstrated that the GBX2 homeobox gene is consistently overexpressed in cultured human prostate cancer cell lines. In this study, the human GBX2 cDNA was cloned and a quantitative reverse transcription-PCR method used to demonstrate that GBX2 mRNA expression is enhanced in approximately 70% of human prostate cancer tissues compared with normal human prostate tissues. Purified recombinant GBX2 protein binds specifically to an ATTA motif within the promoter of the interleukin 6 (IL-6) gene. Using an antisense approach, down-regulation of the expression of GBX2 correlated with decreased expression of IL-6 and an inhibition of tumorigenicity of PC3 human prostate cancer cells. In addition, in vitro growth of the antisense clones was partially restored by exogenous addition of recombinant IL-6 protein to the culture media. These data demonstrated that enhanced GBX2 expression results in a stimulation of malignant growth of prostate cancer cells and that part of this stimulation involves up-regulation in the transcription of the IL-6 gene.
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PMID:Enhanced GBX2 expression stimulates growth of human prostate cancer cells via transcriptional up-regulation of the interleukin 6 gene. 1069 May 29

Overexpression of interleukin 6, a downstream target of the GBX2 homeobox gene, has been linked to the progression of prostate cancer. The Janus kinase-signal transducers and activators of transcription signaling pathway transmits interleukin 6-mediated signals from cell surface receptors to the target genes in the nucleus and is critical in mediating cellular growth and differentiation. We demonstrate that cells derived from both rat and human prostate cancers have constitutively activated Stat3, with Stat3 activation being correlated with malignant potential. Blockade of activated Stat3 by ectopic expression of a dominant-negative Stat3 in human prostate cancer cells significantly suppresses their growth in vitro and their tumorigenicity in vivo. Furthermore, the Janus kinase inhibitor, tyrphostin AG490, inhibited the constitutive activation of Stat3 and suppressed the growth of human prostate cancer cells. These results indicate that activation of Stat3 signaling is essential in the progression of prostate cancer cells and suggest that targeting Stat3 signaling may yield a potential therapeutic intervention for prostate cancer.
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PMID:Inhibition of constitutively activated Stat3 signaling pathway suppresses growth of prostate cancer cells. 1072 80

Gbx2 encodes a DNA-binding transcription factor that plays pivotal roles during embryogenesis. Gain-and loss-of-function studies in several vertebrate species have demonstrated a requirement for Gbx2 in development of the anterior hindbrain, spinal cord, inner ear, heart, and neural crest cells. However, the target genes through which GBX2 exerts its effects remain obscure. Using chromatin immunoprecipitation coupled with direct sequencing (ChIP-Seq) analysis in a human prostate cancer cell line, we identified cis-regulatory elements bound by GBX2 to provide insight into its direct downstream targets. The analysis revealed more than 286 highly significant candidate target genes, falling into various functional groups, of which 51% are expressed in the nervous system. Several of the top candidate genes include EEF1A1, ROBO1, PLXNA4, SLIT3, NRP1, and NOTCH2, as well as genes associated with the Usher syndrome, PCDH15 and USH2A, and are plausible candidates contributing to the developmental defects in Gbx2(-/-) mice. We show through gel shift analyses that sequences within the promoter or introns of EEF1A1, ROBO1, PCDH15, USH2A and NOTCH2, are directly bound by GBX2. Consistent with these in vitro results, analyses of Gbx2(-/-) embryos indicate that Gbx2 function is required for migration of Robo1-expressing neural crest cells out of the hindbrain. Furthermore, we show that GBX2 activates transcriptional activity through the promoter of EEF1A1, suggesting that GBX2 could also regulate gene expression indirectly via EEF1A. Taken together, our studies show that GBX2 plays a dynamic role in development and diseases.
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PMID:Elongation factor 1 alpha1 and genes associated with Usher syndromes are downstream targets of GBX2. 2314 17