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Scientific article
English

Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling

Publication date2004
Abstract

Prostate cancer is the most common solid tumor in men, and it shares with all cancers the hallmark of elevated, nonhomeostatic cell proliferation. Here we have tested the hypothesis that the SONIC HEDGEHOG (SHH)-GLI signaling pathway is implicated in prostate cancer. We report expression of SHH-GLI pathway components in adult human prostate cancer, often with enhanced levels in tumors versus normal prostatic epithelia. Blocking the pathway with cyclopamine or anti-SHH antibodies inhibits the proliferation of GLI1+/PSA+ primary prostate tumor cultures. Inversely, SHH can potentiate tumor cell proliferation, suggesting that autocrine signaling may often sustain tumor growth. In addition, pathway blockade in three metastatic prostate cancer cell lines with cyclopamine or through GLI1 RNA interference leads to inhibition of cell proliferation, suggesting cell-autonomous pathway activation at different levels and showing an essential role for GLI1 in human cells. Our data demonstrate the dependence of prostate cancer on SHH-GLI function and suggest a novel therapeutic approach.

Keywords
  • Cell Division/ physiology
  • DNA-Binding Proteins/metabolism
  • Hedgehog Proteins
  • Humans
  • Kruppel-Like Transcription Factors
  • Male
  • Membrane Proteins/metabolism
  • Nerve Tissue Proteins/metabolism
  • Nuclear Proteins/metabolism
  • Prostate/cytology/metabolism
  • Prostatic Neoplasms/ metabolism/pathology
  • RNA Interference
  • Receptors, Cell Surface
  • Signal Transduction/ physiology
  • Trans-Activators/ metabolism
  • Transcription Factors/genetics/ metabolism
  • Tumor Cells, Cultured
Citation (ISO format)
SANCHEZ, Pilar et al. Inhibition of prostate cancer proliferation by interference with SONIC HEDGEHOG-GLI1 signaling. In: Proceedings of the National Academy of Sciences of the United States of America, 2004, vol. 101, n° 34, p. 12561–12566. doi: 10.1073/pnas.0404956101
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ISSN of the journal0027-8424
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