ATLの高カルシウム血症の分子機構

抄録

PTHrP has been shown to be the main causative factor of humoral hypercalcemia in ATL. It is consitutively over-expressed by ATL tumor cells in vivo. PTHrP gene expression in vivo was shown to be induced by HTLV-1 infection before malignant transformation of the infected cells. Molecular mechanism of induction of this gene expression was investigated by CAT assay with cotransfection of HTLV-1p40^tax expression plasmid and various construct of PTHrPCAT plasmid. Our results indicate that PTHrP promotor is trans-activated by p40^tax, and the responsive element of this transactivation reside within 624bp upstream of transcription start site of exon lb. It is also suggested that zinc finger transcription factor(s) may participate in the transactivation of PTHrP gene expression.