Progressive loss of PAX9 expression correlates with increasing malignancy of dysplastic and cancerous epithelium of the human oesophagus

Abstract

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.

Derivation of a mouse model for conditional inactivation of Pax9

“…Embryos were staged by taking mid-day on the day of vaginal plug detection as embryonic day 0.5 (E0.5). Embryonal heads were embedded in paraffin wax, sectioned, stained with a monoclonal anti-Pax9 antibody, and documented as previously described (Gerber et al, 2002;Kist et al, 2005). Staining of cartilage and bone was performed with alcian blue and alizarin red as described (Kessel et al, 1990).…”

“…A role for Pax9 in epithelial differentiation has been suggested by a study showing that maintenance of PAX9 protein expression in epithelial dysplasia and squamous cell carcinoma of the human esophagus appears to be associated with a favorable outcome (Gerber et al, 2002). However, since Pax9-deficient mice die shortly after birth, the function of Pax9 during late phases of organ development and in tissue homeostasis at postnatal stages is not known.…”

Pax9 mediated cell survival in oral squamous carcinoma cell enhanced by c‐myb

“…The role of Pax9 in epithelial differentiation was suggested in a study which showed that the maintenance of Pax9 protein expression in epithelial dysplasia and squamous cell carcinoma of the human esophagus, appears to be associated with a favorable outcome. 12 However, since Pax9-deficient mice die shortly after birth, the function of Pax9 during the late phases of organ development and in tissue homeostasis in the postnatal stages is unknown.…”

Perplexing Pax: From puzzle to paradigm

“…Human Esophagus *Keratinocytes Normal differentiation process of internal stratified squamous epithelia (esophageal keratinocytes) -increasing malignancy of dysplasias is associated with a progressive loss of PAX9 expression (Gerber et al, 2002) Human Mouse Esophagus Not specified (RNA)** Formation and maintenance of internal stratified squamous epithelium in the anterior digestive tract, which is a different epithelial type to the caudal digestive tract (simple monolayered epithelium) (Peters et al, 1997) Anterior digestive tract *Tongue, oral epithelium, salivary gland, pharynx, esophagus Thymus Not specified (RNA)** Not specified (Neubuser et al, 1995) a Unless indicated analysis indicates in vivo expression in adult differentiated cells and not cell lines or progenitor cells of adult tissue. GWGP, German Waltzing guinea pig.…”