REDUCTION OF ORNITHINE DECARBOXYLASE ANTIZYME (ODC-AZ) LEVEL IN THE 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED HAMSTER BUCCAL POUCH CARCINOGENESIS MODEL

Ornithine decarboxylase (ODC) activity is elevated in and necessary fo r oral carcinogenesis, but the mechanism for its deregulation is uncle ar. Using subtractive hybridization, a 1029 bp full-length cDNA encodi ng a 222 amino acid open reading frame has been isolated from normal h amster oral keratinocytes. The hamster cDNA is homologous to the human , mouse and rat ornithine decarboxylase antizyme gene (ODC-Az). The ha mster ODC-Az gene demonstrated a restriction fragment length polymorph ism (RFLP) upon Southern blot analysis comparing normal and tumor hams ter genomic DNA. Northern blot analysis revealed that normal hamster o ral keratinocytes express readily detectable level of ODC-Az mRNA. Mal ignant oral keratinocytes demonstrate reduced expression of the ODC-Az mRNA, In contrast, malignant hamster oral keratinocytes have elevated ODC mRNA levels and lengthened ODC protein half-life when compared to the normal counterparts, This mas corroborated by direct measurement of ODC enzymatic activity. These data support the hypothesis that the reduced and/or loss of expression and function of the ODC-Az gene is a n important event for the early de-regulation of cellular proliferatio n during oral tumor development.