Insulin-like growth factor (IGF) system components in human prostatic cancer cell-lines: LNCaP, DU145, and PC-3 cells

Int J Urol. 1996 Jan;3(1):39-46. doi: 10.1111/j.1442-2042.1996.tb00628.x.

Abstract

Background: Evidence has been accumulating that in many tumors, insulin-like growth factors (IGFs) promote cancer cell growth in an autocrine/paracrine manner via the IGF-I receptor. In an effort to understand the role of IGFs in prostate cancer cell growth, we characterized the IGF system components produced by human prostatic cancer cell-lines, LNCaP, DU145, and PC-3, grown in serum-free medium.

Methods: IGFs, their receptors, and IGF binding proteins (IGFBPs) produced by the three human prostate cell lines were characterized by reverse transcriptase-polymerase chain reaction (RT-PCR), radioimmunoassay (RIA), Western ligand blot, Western immunoblot, and Northern blot analyses.

Results: mRNA for IGF-II and receptors for IGF-I and IGF-II were detected in all three cell-lines by RT-PCR. In contrast to the published study, only LNCaP cells expressed a trace amount of IGF-I mRNA. RIA on conditioned media collected from these cells revealed that all three cell-lines produced measurable IGF-II but not IGF-I. Western Ligand blot, Western immunoblot, and Northern blot analyses revealed that LNCaP, DU145, and PC-3 cells expressed IGFBP-2, IGFBP-2/-3/-4/-6, and IGFBP-2/-3/-4/-5/-6, respectively. IGF-II stimulated [3H]thymidine incorporation into DNA in DU145 and PC-3 cells significantly although the effect was small. DNA synthesis in PC-3 cells but not in LNCaP and DU145 cells was significantly inhibited by the IGF-I receptor-specific monoclonal antibody.

Conclusion: Theses results suggest potentially important roles of IGFs and IGFBPs in prostate cancer cell growth, and that in particular, IGF-II may play a critical role in prostate cancer cell growth.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Base Sequence
  • Blotting, Northern
  • Cell Division / drug effects
  • Cell Division / immunology
  • Culture Media, Conditioned / chemistry
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3 / analysis
  • Insulin-Like Growth Factor Binding Protein 3 / genetics
  • Insulin-Like Growth Factor Binding Protein 4 / genetics
  • Insulin-Like Growth Factor Binding Protein 4 / metabolism
  • Insulin-Like Growth Factor Binding Protein 5 / genetics
  • Insulin-Like Growth Factor Binding Protein 5 / metabolism
  • Insulin-Like Growth Factor Binding Protein 6 / genetics
  • Insulin-Like Growth Factor Binding Protein 6 / metabolism
  • Insulin-Like Growth Factor Binding Proteins / analysis
  • Insulin-Like Growth Factor Binding Proteins / genetics
  • Insulin-Like Growth Factor Binding Proteins / metabolism
  • Insulin-Like Growth Factor I / analysis
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor II / analysis
  • Insulin-Like Growth Factor II / genetics*
  • Insulin-Like Growth Factor II / pharmacology
  • Male
  • Molecular Sequence Data
  • Prostatic Neoplasms*
  • RNA, Messenger / analysis
  • Receptor, IGF Type 1 / analysis
  • Receptor, IGF Type 1 / genetics*
  • Receptor, IGF Type 1 / metabolism
  • Receptor, IGF Type 2 / analysis
  • Receptor, IGF Type 2 / genetics*
  • Receptor, IGF Type 2 / metabolism
  • Tumor Cells, Cultured / chemistry
  • Tumor Cells, Cultured / cytology
  • Tumor Cells, Cultured / physiology

Substances

  • Antibodies, Monoclonal
  • Culture Media, Conditioned
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Protein 4
  • Insulin-Like Growth Factor Binding Protein 5
  • Insulin-Like Growth Factor Binding Protein 6
  • Insulin-Like Growth Factor Binding Proteins
  • RNA, Messenger
  • Receptor, IGF Type 2
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II
  • Receptor, IGF Type 1