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Gene expression profiles of PNT1a prostate cells expressing FGFR-4 Arg388 or Gly388.

ABSTRACT: We have shown that in PNT1a cells expressing exogenous FGFR4 Arg388 or Gly388 under the control of the EF1 promoter almost all FGFR signaling can be attributed to the transfected receptor, and the two FGFR-4 isoforms are expressed at equivalent levels in the two cell lines. Furthermore, we have shown that serum contains abundant FGFs capable of activating FGFR-4 so these initial experiments were carried out in serum to mimic physiological conditions. In such conditions the Arg388 expressing PNT1a cells display increased invasiveness and motility compared to Gly388 expressing cells. FGFR-4 Arg388 allele shows increased receptor stability and sustained receptor activation following ligand binding when compared to the Gly388 allele. However, the impact of this sustained signaling on cellular signal transduction pathways is unknown. We therefore analyzed the effect of FGFR-4 Arg388 expression on signal transduction in prostatic epithelial cells. We have found that expression of the FGFR-4 Arg388 allele leads to increased activity of the MAPK pathway, increased activity of serum response factor and AP1 and transcription of multiple genes which are correlated with aggressive clinical behavior in prostate cancer. Keywords: two group comparison

ORGANISM(S): Homo sapiens

PROVIDER: GSE20906 | GEO | 2011/07/01

SECONDARY ACCESSION(S): PRJNA124407

REPOSITORIES: GEO

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Gene expression profiles of PNT1a prostate cells expressing FGFR-4 Arg388 or Gly388.

Project description:We have shown that in PNT1a cells expressing exogenous FGFR4 Arg388 or Gly388 under the control of the EF1 promoter almost all FGFR signaling can be attributed to the transfected receptor, and the two FGFR-4 isoforms are expressed at equivalent levels in the two cell lines. Furthermore, we have shown that serum contains abundant FGFs capable of activating FGFR-4 so these initial experiments were carried out in serum to mimic physiological conditions. In such conditions the Arg388 expressing PNT1a cells display increased invasiveness and motility compared to Gly388 expressing cells. FGFR-4 Arg388 allele shows increased receptor stability and sustained receptor activation following ligand binding when compared to the Gly388 allele. However, the impact of this sustained signaling on cellular signal transduction pathways is unknown. We therefore analyzed the effect of FGFR-4 Arg388 expression on signal transduction in prostatic epithelial cells. We have found that expression of the FGFR-4 Arg388 allele leads to increased activity of the MAPK pathway, increased activity of serum response factor and AP1 and transcription of multiple genes which are correlated with aggressive clinical behavior in prostate cancer. Keywords: two group comparison To further understand the underlying molecular mechanisms of increased cell motility and invasiveness in Arg388 expressing cells, microarray studies of biological duplicates were performed on FGFR4 Arg388 and Gly388 expressing PNT1a cells using Agilent 44k whole genome expression microarrays to identify the effector genes that may be responsible for phenotypic differences between the two variants.

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Homo sapiens

Project description:Gene expression profiles of PNT1a prostate cells expressing FGFR-4 Arg388 or Gly388.

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