REGULATION OF PARATHYROID HORMONE-RELATED PROTEIN EXPRESSION IN A CANINE SQUAMOUS CARCINOMA CELL-LINE BY COLCHICINE

The regulation of parathyroid hormone-related protein expression by co lchicine, vinblastine, nocodazole, taxol, transforming growth factor-b eta 1 (TGF beta 1), and epidermal growth factor (EGF) was investigated in a canine squamous carcinoma cell line (SCC 2/88 cells). SCC 2/88 c ells were stably transfected with a human P2/P3 PTHrP promoter-lucifer ase reporter gene construct and gene expression was measured after che mical treatments. The greatest increase in reporter gene expression wa s observed after colchicine treatment and small increases occurred aft er treatment with vinblastine, taxol, TGF beta 1, or EGF. Nocodazole h ad no significant effect on reporter gene expression. Colchicine also increased PTHrP steady state mRNA expression and PTHrP secretion by SC C 2/88 cells. These results demonstrated that PTHrP production was inc reased in SCC2/88 cells by colchicine and suggested that factors or ev ents during mitosis are capable of stimulating PTHrP production. An in crease in PTHrP production during mitosis of malignant epithelial cell s may be important in the pathogenesis of humoral hypercalcemia of mal ignancy.