Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus.
Pax genes encode a family of transcription factors that play key roles in embryonic development. Whereas the functions of Pax genes in the adult organism are largely unknown, upregulated Pax gene expression has been implicated in tumourigenesis. In this study, PAX9-specific monoclonal antibodies have been generated and it has been shown that PAX9 protein is expressed in the normal epithelium of the adult human oesophagus. PAX9 expression was either lost or significantly reduced in the majority of invasive carcinomas and epithelial dysplasias, the latter representing precancerous lesions. Notably, the percentage of PAX9-positive cells within the epithelium decreased with increasing malignancy of the epithelial lesion. These results identify PAX9 as a sensitive marker for deregulated differentiation of oesophageal keratinocytes and indicate a role for PAX9 in the normal differentiation process of internal stratified squamous epithelia. These data suggest that upregulated PAX9 expression is not required for the formation of the majority of squamous cell carcinomas of the human oesophagus.
Gerber
Josef-Karl
JK
Institute of Experimental Genetics, GSF-National Research Centre for Environment and Health, Neuherberg, Germany.
Richter
Thomas
T
Kremmer
Elisabeth
E
Adamski
Jerzy
J
Höfler
Heinz
H
Balling
Rudi
R
Peters
Heiko
H
D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000032:analysis*; D004848:Epithelium / Q000737:chemistry; D004938:Esophageal Neoplasms / Q000737:chemistry* / Q000473:pathology; D004947:Esophagus / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D015603:Keratinocytes / Q000737:chemistry; D051764:PAX9 Transcription Factor; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000032:analysis*
D015415:Biomarkers; D004268:DNA-Binding Proteins; D051764:PAX9 Transcription Factor; C497323:PAX9 protein, human; D014157:Transcription Factors