Activation of the hedgehog pathway in a subset of lung cancers

• Published in: Cancer letters Vol. 244; no. 1; pp. 53 - 60
• Main Authors: Chi, Sumin, Huang, Shuhong, Li, Chengxin, Zhang, Xiaoli, He, Nonggao, Bhutani, Manoop S., Jones, Dennie, Castro, Claudia Y., Logrono, Roberto, Haque, Abida, Zwischenberger, Joseph, Tyring, Stephen K., Zhang, Hongwei, Xie, Jingwu
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28.11.2006; Elsevier Limited
• Subjects: 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 culture; Cell Proliferation; Colony-Forming Units Assay; Female; Gli1; Hedgehog; Hedgehog Proteins - genetics; Hedgehog Proteins - metabolism; Humans; Hybridization; Immunoblotting; Immunoenzyme Techniques; In Situ Hybridization; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Mortality; Mutation; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Patched Receptors; Pathology; Patients; Proteins; PTCH1; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; RNA, Neoplasm - genetics; RNA, Neoplasm - metabolism; Signal Transduction; Su(Fu); Trans-Activators - genetics; Trans-Activators - metabolism; Tumor Cells, Cultured; Tumors; Zinc Finger Protein GLI1; China; Hedgehog; Su(Fu); shh; BCC; NSCLC; Lung cancer; PTCH1; Gli1; PTC
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2005.11.036

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.