Biomaterial Database

[Activation of sonic hedgehog signaling in keratocystic odontogenic tumors]. 2009

K Freier, and S Pungs, and C Flechtenmacher, and C Hofele

Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitätsklinikum Heidelberg, Heidelberg. Kolja.Freier@med.uni-heidelberg.de

BACKGROUND Keratocystic odontogenic tumors are benign neoplasms of the viscerocranium that occur sporadically as well as in association with Gorlin-Goltz syndrome. Multiple basal cell carcinomas of the skin are another typical feature of Gorlin-Goltz syndrome. Aberrant activation of sonic hedgehog signaling has been reported for sporadic and hereditary basal cell carcinoma caused by specific genetic mutations, but for keratocystic odontogenic tumors, the role of aberrant sonic hedgehog signaling has not yet been evaluated in detail. METHODS In the present study, 131 keratocystic odontogenic tumors were analyzed by immunohistochemistry for the expression of sonic hedgehog signaling proteins SHH, PTCH1, SMO, GLI1, and NMYC on tissue microarray sections. RESULTS High expression of the analyzed proteins-between 67.3% (PTCH1) and 92.9% (SHH)-was found in the epithelial compartment of the keratocystic odontogenic tumors analyzed. In the stromal compartment of the tumors, high expression of the target proteins was found significantly less frequently (all p-values <0.001). CONCLUSIONS Aberrant sonic hedgehog signaling is critically involved in the molecular pathogenesis of keratocystic odontogenic tumors. This finding underlines the neoplastic character of this intraosseous lesion. Because of high recurrence rates after local excision, more radical surgical approaches are recommended for treating keratocystic odontogenic tumors.

UI	MeSH Term	Description	Entries
D007573	Jaw Neoplasms	Cancers or tumors of the MAXILLA or MANDIBLE unspecified. For neoplasms of the maxilla, MAXILLARY NEOPLASMS is available and of the mandible, MANDIBULAR NEOPLASMS is available.	Cancer of Jaw,Jaw Cancer,Cancer of the Jaw,Neoplasms, Jaw,Cancer, Jaw,Cancers, Jaw,Jaw Cancers,Jaw Neoplasm,Neoplasm, Jaw
D009807	Odontogenic Cysts	Cysts found in the jaws and arising from epithelium involved in tooth formation. They include follicular cysts (e.g., primordial cyst, dentigerous cyst, multilocular cyst), lateral periodontal cysts, and radicular cysts. They may become keratinized (odontogenic keratocysts). Follicular cysts may give rise to ameloblastomas and, in rare cases, undergo malignant transformation.	Keratocysts,Cyst, Odontogenic,Cysts, Odontogenic,Keratocyst,Odontogenic Cyst
D009808	Odontogenic Tumors	Neoplasms produced from tooth-forming tissues.	Neoplasms, Dental Tissue,Dental Tissue Neoplasms,Dental Tissue Neoplasm,Neoplasm, Dental Tissue,Odontogenic Tumor,Tissue Neoplasm, Dental,Tissue Neoplasms, Dental,Tumor, Odontogenic,Tumors, Odontogenic
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014407	Tumor Cells, Cultured	Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.	Cultured Tumor Cells,Neoplastic Cells, Cultured,Cultured Neoplastic Cells,Cell, Cultured Neoplastic,Cell, Cultured Tumor,Cells, Cultured Neoplastic,Cells, Cultured Tumor,Cultured Neoplastic Cell,Cultured Tumor Cell,Neoplastic Cell, Cultured,Tumor Cell, Cultured
D015398	Signal Transduction	The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.	Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D015972	Gene Expression Regulation, Neoplastic	Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.	Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D053823	Hedgehog Proteins	A family of intercellular signaling proteins that play an important role in regulating the development of many TISSUES and organs. Their name derives from the observation of a hedgehog-like appearance in DROSOPHILA embryos with genetic mutations that block their action.	Hedgehog Protein,Hedgehog Protein, Vertebrate,Banded Hedgehog Protein,Desert Hedgehog Protein,Indian Hedgehog Protein,Sonic Hedgehog Protein,Vertebrate Hedgehog Protein,Hedgehog Protein, Banded,Hedgehog Protein, Desert,Hedgehog Protein, Indian,Hedgehog Protein, Sonic,Protein, Hedgehog