mRNA expression and phenotype of odontogenic tumours in the v-Ha-ras transgenic mouse.
Ameloblastomas are the most common odontogenic neoplasia in humans, and although typically considered locally invasive and benign, frequently recur subsequent to surgical resection. The Tg.AC transgenic mouse carrying the v-Ha-ras oncogene has been found to spontaneously develop ameloblastoma-like tumours (35% by 1 year of age) that are rare in the wild type FVB background strain.


OBJECTIVE
The purpose of this study was to characterise the mRNA expression of genes in the mouse tumours that are either expressed in human ameloblastomas or essential for normal odontogenesis and to correlate the expression to the histological phenotype.


METHODS
Histological, immunohistochemical and RT-PCR studies were used to evaluate clinically demonstrable odontogenic tumours occurring spontaneously in seven Tg.AC v-Ha-ras transgenic mice (homozygous, at 7 months of age or heterozygous at 11 months of age).


RESULTS
Most genes profiled were expressed in all tumour samples, however three (amelogenin, matrix metalloproteinase-20 (MMP-20) and Dlx7) displayed differential expression. In addition, only the most highly differentiated tumour stained positively for collagen. In most cases, the variable expression could be explained by reference to the histological phenotype, although differences in gene expression were apparent within the Type 2 and the mixed phenotype tumours.


CONCLUSIONS
These data confirm that many of the genes thought to be important in odontogenesis and odontogenic tumour formation in humans are also expressed in these murine ameloblastoma-like tumours however genes associated with terminal differentiation of ameloblasts demonstrate differential expression between the tumour phenotypes.
Dodds
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Department Pediatric Dentistry, UNC School of Dentistry, University of North Carolina at Chapel Hill, Manning Drive, Chapel Hill, NC 27599, USA. anne_dodds@dentistry.unc.edu
Cannon
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Suggs
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Wright
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JT
D000564:Ameloblastoma / Q000378:metabolism* / Q000473:pathology; D053523:Amelogenin; D000818:Animals; D002454:Cell Differentiation; D003746:Dental Enamel Proteins / Q000032:analysis / Q000235:genetics; D015870:Gene Expression; D011905:Genes, ras; D018398:Homeodomain Proteins / Q000032:analysis / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D007573:Jaw Neoplasms / Q000378:metabolism* / Q000473:pathology; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases / Q000032:analysis / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009363:Neoplasm Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors
D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins; C104149:Dlx4 protein, mouse; D018398:Homeodomain Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C507111:MMP20 protein, human; D053519:Matrix Metalloproteinase 20; D020782:Matrix Metalloproteinases; C507113:Mmp20 protein, mouse