Hedgehog signaling in small-cell lung cancer: frequent in vivo but a rare event in vitro

Lung Cancer. 2006 Jun;52(3):281-90. doi: 10.1016/j.lungcan.2005.12.014. Epub 2006 Apr 17.


The hedgehog (HH) signaling pathway plays multiple roles during embryonic development and increasing evidence suggests that this embryonic pathway is involved in development and progression of several human cancers including those of the brain, skin, lung and gastrointestinal tract. To investigate HH signaling activity in small-cell lung cancer (SCLC), we have performed gene expression analysis on members of the HH pathway on a panel of 20 SCLC cell lines. Sonic hedgehog (SHH) expression was detected in only DMS79 and GLC16 and only DMS114 expressed detectable protein levels of GLI1, one of the key transcription factors of the pathway. Involvement of HH signaling in SCLC proliferation was investigated in a subset of cell lines using the HH signaling inhibitor cyclopamine or small interfering RNA (siRNA) against GLI1. Cells expressing GLI1 responded only weakly to both cyclopamine and RNA interference, suggesting that HH signaling plays only a minor role in the growth of SCLC cell lines. To investigate HH pathway activity in vivo, GLI1 immunohistochemistry was performed on SCLC tumors. Interestingly, GLI1 was expressed in most SCLC tumors studied, indicating that HH signaling is important for in vivo growth of SCLC but establishment of cell lines from SCLC tumors may lead to loss of expression of key HH pathway members. Thus, the data support the idea that the HH pathway may be a therapeutic target in SCLC. However, the data also suggest that the SCLC cells can circumvent the apparent in vivo requirement of HH signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Small Cell / drug therapy
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Gene Expression Regulation, Neoplastic* / genetics
  • Hedgehog Proteins
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Oncogene Proteins / biosynthesis
  • Oncogene Proteins / genetics
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Signal Transduction* / drug effects
  • Signal Transduction* / genetics
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Veratrum Alkaloids / pharmacology
  • Zinc Finger Protein GLI1


  • Hedgehog Proteins
  • Oncogene Proteins
  • RNA, Small Interfering
  • SHH protein, human
  • Trans-Activators
  • Veratrum Alkaloids
  • Zinc Finger Protein GLI1
  • cyclopamine