Parathyroid hormone-related protein enhances PC-3 prostate cancer cell growth via both autocrine/paracrine and intracrine pathways.

Abstract

Parathyroid hormone-related protein (PTHrP) is expressed by human prostatic tissue and prostate cancer cell lines, and positively influences primary prostate tumor growth in vivo. The human prostate cancer cell line PC-3, which expresses functional PTH/PTHrP receptors, was used as a model to study the effects of PTHrP on prostate cancer cell growth. Addition of PTHrP (1-34), (1-86), and (1-139) increased cell number and [3H]thymidine incorporation; these effects were reversed by anti-PTHrP antiserum. This antiserum also decreased endogenous PC-3 cell growth. Clonal PTHrP-overexpressing PC-3 cell lines also showed enhanced cell growth and [3H]thymidine incorporation and were enriched in the G2+M phase of the cell cycle, suggesting an effect of PTHrP on mitosis. Overexpression of PTHrP with the nuclear localization sequence (NLS) deletion partially reversed the growth-stimulatory effects. The growth rate of these cells was midway between that of wild-type PTHrP-overexpressing and control cells, presumably because NLS-mutated PTHrP is still secreted and acts through the cell surface PTH/PTHrP receptor. In contrast to NLS-mutated PTHrP, wild-type protein showed preferential nuclear localization. These results suggest that the proliferative effects of PTHrP in PC-3 cells are mediated via both autocrine/paracrine and intracrine pathways, and that controlling PTHrP production in prostate cancer may be therapeutically beneficial.

• Authors: Veronica A Tovar Sepulveda, Miriam Falzon
• Journal: Regulatory peptides (Regul Pept) Vol. 105 Issue 2 Pg. 109-20 (May 15 2002) ISSN: 0167-0115 [Print] Netherlands
• PMID: 11891011 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Nuclear Localization Signals
• PTHLH protein, human
• Parathyroid Hormone
• Parathyroid Hormone-Related Protein
• Peptide Fragments
• Peptides
• Proteins
• parathyroid hormone-related protein (1-16)
• parathyroid hormone-related protein (1-86)
• parathyroid hormone-related protein (1-34)
• parathyroid hormone-related protein (107-139)

Topics

• Autocrine Communication (physiology)
• Cell Division (drug effects)
• Cell Nucleus (metabolism)
• G2 Phase
• Humans
• Male
• Mitosis
• Neutralization Tests
• Nuclear Localization Signals (metabolism)
• Paracrine Communication (physiology)
• Parathyroid Hormone (genetics)
• Parathyroid Hormone-Related Protein
• Peptide Fragments (metabolism, pharmacology)
• Peptides (metabolism, pharmacology)
• Prostatic Neoplasms
• Proteins (genetics, metabolism, pharmacology)
• Signal Transduction
• Tumor Cells, Cultured