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Upregulated FGFR1 expression is associated with the transition of hormone-naive to castrate-resistant prostate cancer.

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  • معلومة اضافية
    • المصدر:
      Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE
    • بيانات النشر:
      Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
      Original Publication: London, Lewis.
    • الموضوع:
      Castration*; Androgen Antagonists/*pharmacology ; Gonadotropin-Releasing Hormone/*pharmacology ; Prostatic Neoplasms/*genetics ; Receptor, Fibroblast Growth Factor, Type 1/*genetics; Aged ; Aged, 80 and over ; Cell Line, Tumor ; Gene Expression Profiling ; Humans ; Male ; Middle Aged ; Neoplasms, Hormone-Dependent/genetics ; Orchiectomy ; Receptors, Androgen/genetics ; Recurrence ; Signal Transduction ; Up-Regulation
    • نبذة مختصرة :
      Background: Prostate cancer (PC) represents a global health issue. Treatment for locally advanced and metastatic PC remains unsatisfactory. The androgen receptor (AR) has been validated in having a key role in both naïve and castrate-resistant PC (CRPC). However, the significance of other signalling pathways in CRPC is less well validated.
      Methods: To gain a better insight into the molecular signalling cascades involved in clinical CRPC, we performed gene expression profiling using the Illumina DASL assay and studied matched hormone-naive (HN) and CR prostate tumours (n=10 pairs). Ingenuity Pathways Analysis (IPA) was used to identify potential networks involved, and further validation was performed in in vitro cell models and clinical tumours.
      Results: Expression of 50 genes was significantly different between HN and CRPC. IPA revealed two networks of particular interest, including AR and FGFR1, respectively. FGFR1 expression was confirmed to be significantly upregulated in CRPC (P ≤ 0.005), and abnormal FGFR1 expression was associated with shorter time to biochemical relapse in HNPC (P=0.006) and less favourable disease-specific survival in CRPC (P=0.018).
      Conclusion: For the first time, our gene expression profiling experiment on archival tumour materials has identified upregulated FGFR1 expression to be associated with PC progression to the CR state.
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    • Grant Information:
      15151 United Kingdom CRUK_ Cancer Research UK; G0802141 United Kingdom MRC_ Medical Research Council; G0900871 United Kingdom MRC_ Medical Research Council
    • الرقم المعرف:
      0 (Androgen Antagonists)
      0 (Receptors, Androgen)
      33515-09-2 (Gonadotropin-Releasing Hormone)
      EC 2.7.10.1 (FGFR1 protein, human)
      EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1)
    • الموضوع:
      Date Created: 20110929 Date Completed: 20111214 Latest Revision: 20240821
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC3241546
    • الرقم المعرف:
      10.1038/bjc.2011.367
    • الرقم المعرف:
      21952621