Overexpression of parathyroid hormone-related protein promotes cell growth in the rat intestinal cell line IEC-6.
The rat intestinal cell line, IEC-6, was used as a model to study effects of parathyroid hormone-related protein (PTHrP) on crypt cell growth. Studies showed that addition of PTHrP analogs (1-34), (67-86), or (107-139) to growth 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 IEC-6 cells stably transfected with PTHrP cDNA and overexpressing PTHrP showed that increased PTHrP production enhanced cell growth and 3H-thymidine incorporation in high, but not low, serum. Additional studies examined the role of the nuclear localization sequence (NLS) of PTHrP in mediating the growth effect. In three clonal IEC-6 lines transfected with PTHrP cDNA bearing a mutated NLS, the ability of PTHrP to stimulate 3H-thymidine incorporation and cell growth was lost. The results suggest that endogenously produced PTHrP can promote proliferation of IEC-6 cells and that the integrity of the NLS of PTHrP is required for its growth effects.
Ye
Y
Y
Department of Pharmacology and Toxicology, The University of Texas Medical Branch, Galveston, TX 77555-1031, USA.
Falzon
M
M
Seitz
P K
PK
Cooper
C W
CW
D000818:Animals; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D005822:Genetic Vectors / Q000138:chemical synthesis; D006801:Humans; D019913:Nuclear Localization Signals / Q000235:genetics; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology; D051381:Rats; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection
D019913:Nuclear Localization Signals; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); C071097:parathyroid hormone-related protein (107-139)