title: Parathyroid hormone-related protein: a potential autocrine growth regulator in human prostate cancer cell lines.
abstract: OBJECTIVE
  We recently demonstrated that parathyroid hormone-related protein (PTHrP) is widely expressed by human prostate cancer tissue, suggesting that PTHrP might be involved in the growth and development of prostate cancer. To study this further, the production of PTHrP and its biologic effect were investigated using human prostate cancer cell lines.
  
  
  METHODS
  The cell lines used were one androgen-dependent cell line, LNCaP, and two androgen-independent cell lines, PC-3 and DU-145. PTHrP secreted by cancer cells was measured by radioimmunoassay. The effect of PTHrP on DNA synthesis in these cells was determined by thymidine incorporation assay.
  
  
  RESULTS
  All cell lines secreted immunodetectable levels of PTHrP in the culture-conditioned media. PC-3 cells secreted significantly higher amounts than the other two cell lines. A synthetic peptide, PTHrP(1-34), stimulated thymidine uptake in PC-3 and DU-145 cells more than threefold the control under serum-free and steroid-free conditions, whereas LNCaP was not affected. However, in the presence of dihydrotestosterone, DNA synthesis of LNCaP cells was stimulated by PTHrP in a dose-dependent manner. Additionally, this PTHrP-induced DNA synthesis was completely neutralized by a validated mouse monoclonal antibody (8B12) raised against PTHrP(1-34).
  
  
  CONCLUSIONS
  Our data suggest that PTHrP may play a significant role in the growth of prostate cancer by acting locally in an autocrine fashion.
authors.affiliation: Department of Urology, University of Rochester, New York.
authors.forename: M
authors.initials: M
authors.lastname: Iwamura
authors.forename: P A
authors.initials: PA
authors.lastname: Abrahamsson
authors.forename: K A
authors.initials: KA
authors.lastname: Foss
authors.forename: G
authors.initials: G
authors.lastname: Wu
authors.forename: A T
authors.initials: AT
authors.lastname: Cockett
authors.forename: L J
authors.initials: LJ
authors.lastname: Deftos
mesh_terms: D004273:DNA, Neoplasm / Q000096:biosynthesis; D006133:Growth Substances / Q000096:biosynthesis* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D010281:Parathyroid Hormone / Q000096:biosynthesis* / Q000502:physiology; D044162:Parathyroid Hormone-Related Protein; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D014176:Protein Biosynthesis; D011506:Proteins / Q000502:physiology; D011863:Radioimmunoassay; D014407:Tumor Cells, Cultured / Q000378:metabolism
chemical_list: D004273:DNA, Neoplasm; D006133:Growth Substances; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D011506:Proteins