Document Detail

Mutations in the human homologue of the Drosophila segment polarity gene patched in oral squamous cell carcinoma cell lines.
MedLine Citation:
PMID:  11573822     Owner:  NLM     Status:  MEDLINE    
In the present study, we have analyzed tumor deoxyribonucleic acid from oral squamous cell carcinoma (OSCC) cells for patched mutations using an exon-by-exon single strand conformation polymorphism assay and direct sequencing. We found two missense mutations which affected the conserved residue in the transmembrane domains of the gene product and in the intracellular loop at the C-terminal residue implicated in regulating the smoothened molecule. In addition, we demonstrated that the N-terminal fragment of sonic hedgehog (Shh-N) stimulates the growth of normal epithelial cells, the OSCC cell line, NA, and the salivary gland adenocarcinoma cell lines, HSG and HSY, which have no detectable mutation in patched. On the other hand, Shh has no effect on human SCC cells (UE, KA, KO, NI, A431 cells) that have mutations in patched. These results strongly suggest that an Shh-patched signaling is involved in the cell growth of oral epithelial cells and in the tumorigenesis of OSCCs.
E Michimukai; N Kitamura; Y Zhang; H Wang; Y Hiraishi; K Sumi; Y Hayashido; S Toratani; T Okamoto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  In vitro cellular & developmental biology. Animal     Volume:  37     ISSN:  1071-2690     ISO Abbreviation:  In Vitro Cell. Dev. Biol. Anim.     Publication Date:    2001 Jul-Aug
Date Detail:
Created Date:  2001-09-27     Completed Date:  2002-02-08     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9418515     Medline TA:  In Vitro Cell Dev Biol Anim     Country:  United States    
Other Details:
Languages:  eng     Pagination:  459-64     Citation Subset:  IM    
Department of Molecular Oral Medicine & Maxillofacial Surgery 1, Hiroshima University Faculty of Dentistry, Japan.
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MeSH Terms
Carcinoma, Squamous Cell / genetics*
Cell Division / drug effects
Culture Media, Serum-Free
DNA Mutational Analysis
DNA, Neoplasm / analysis*
Epithelial Cells / drug effects
Hedgehog Proteins
Membrane Proteins / genetics*
Mouth Neoplasms / genetics*
Mutation, Missense
Peptide Fragments / pharmacology
Polymorphism, Single-Stranded Conformational
RNA, Messenger / analysis
Receptors, Cell Surface
Sequence Analysis, DNA
Signal Transduction
Trans-Activators / pharmacology
Tumor Cells, Cultured
Reg. No./Substance:
0/Culture Media, Serum-Free; 0/DNA, Neoplasm; 0/Hedgehog Proteins; 0/Membrane Proteins; 0/Peptide Fragments; 0/RNA, Messenger; 0/Receptors, Cell Surface; 0/SHH protein, human; 0/Trans-Activators; 0/patched receptors

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