Activation of the hedgehog pathway in a subset of lung cancers

Cancer Lett. 2006 Nov 28;244(1):53-60. doi: 10.1016/j.canlet.2005.11.036. Epub 2006 Jan 30.

Abstract

Activation of the hedgehog pathway is reported in lung cancer, but its frequency remains unknown. We examine activation of this pathway in lung cancers by in situ hybridization and immunohistochemstry, and find that less than 10% of the tumors have elevated hedgehog target gene expression. We further identify a cell line NCI-H209 and two primary tumors with no detectable Su(Fu), a negative regulator of the pathway. Ectopic expression of Su(Fu) in NCI-H209 cells down-regulates hedgehog target gene expression and leads to inhibition of cell proliferation. These data indicate that activation of the hedgehog pathway is activated through Shh over-expression or Su(Fu) inactivation in only a subset of lung cancers.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Blotting, Northern
  • Blotting, Western
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / metabolism
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / metabolism
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cell Proliferation
  • Colony-Forming Units Assay
  • Female
  • Hedgehog Proteins / genetics
  • Hedgehog Proteins / metabolism*
  • Humans
  • Immunoblotting
  • Immunoenzyme Techniques
  • In Situ Hybridization
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Male
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Patched Receptors
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Signal Transduction*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Tumor Cells, Cultured
  • Zinc Finger Protein GLI1

Substances

  • Hedgehog Proteins
  • Oncogene Proteins
  • Patched Receptors
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Repressor Proteins
  • SUFU protein, human
  • Trans-Activators
  • Zinc Finger Protein GLI1