Overexpression of parathyroid hormone-related protein promotes cell growthin the rat intestinal cell line IEC-6

The rat intestinal cell line. IEC-6, was used as a model to study effects o f parathyroid hormone-related protein (PTHrP) on crypt cell growth. Studies showed that addition of PTHrP analogs (1-34), (67-86), or (107-139) to gro wth medium did not affect proliferation of cells grown in either high (10% Nu-Serum) or low serum (1% Nu-Serum). However, studies on clonal lines of I EC-6 cells stably transfected with PTHrP cDNA and overexpressing PTHrP show ed that increased PTHrP production enhanced cell growth and H-3-thymidine i ncorporation in high, but not low, serum. Additional studies examined the r ole of the nuclear localization sequence (NLS) of PTHrP in mediating the gr owth effect. In three clonal IEC-6 lines transfected with PTHrP cDNA bearin g a mutated NLS, the ability of PTHrP to stimulate 3H-thymidine incorporati on and cell growth was lost. The results suggest that endogenously produced PTHrP can promote proliferation of IEC-6 cells and that the integrity of t he NLS of PTHrP is required for its growth effects. (C) 2001 Elsevier Scien ce B.V. All rights reserved.