Activation of the hedgehog pathway in a subset of lung cancers.
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.
Chi
Sumin
S
Department of Pharmacology, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1048, USA.
Huang
Shuhong
S
Li
Chengxin
C
Zhang
Xiaoli
X
He
Nonggao
N
Bhutani
Manoop S
MS
Jones
Dennie
D
Castro
Claudia Y
CY
Logrono
Roberto
R
Haque
Abida
A
Zwischenberger
Joseph
J
Tyring
Stephen K
SK
Zhang
Hongwei
H
Xie
Jingwu
J
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D003114:Colony-Forming Units Assay; D005260:Female; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000072079:Patched Receptors; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000071676:Zinc Finger Protein GLI1
D053823:Hedgehog Proteins; D015513:Oncogene Proteins; D000072079:Patched Receptors; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D012097:Repressor Proteins; C490764:SUFU protein, human; D015534:Trans-Activators; D000071676:Zinc Finger Protein GLI1