Platelet-derived growth factor induces proliferation of hyperplastic human prostatic stromal cells.
Prostatic hyperplasia (BPH) is a very common disease in elderly men and is characterized by abnormal proliferation of the stromal and epithelial cells of the prostate. The observation that BPH often occurs in association with chronic inflammation has led to the examination of the possibility that platelet-derived growth factor (PDGF), which is released in response to inflammation, may be an etiological factor in the genesis of the disease. It has been shown that cultured cells derived from human prostatic tissue express high affinity PDGF-beta receptors based on receptor binding and cross-linking studies with [125I]-PDGF-BB. The experiments presented below demonstrate that PDGF receptors are activated in response to the growth factor and that mitogenesis is induced. PDGF-BB treatment of cultured human prostate cells derived from patients with BPH activates the signal transduction pathway of the PDGF receptor as shown by the presence of several phosphoproteins in antiphosphotyrosine immunoprecipitates, including autophosphorylation of the PDGF receptor. Phosphatidylinositol (PI) 3-kinase activity is also increased in cells stimulated with PDGF. The addition of PDGF-BB to the medium causes of variable but dose-dependent increase in [3H]-thymidine incorporation. This paper describes the first demonstration that PDGF is a potent mitogen for human cells derived from patients exhibiting prostatic hyperplasia, and also demonstrates that the cellular response to PDGF-BB is heterogenous in a manner that is consistent with the varying degree of hyperplasia and inflammation clinically and histologically in the tissue specimens.
Vlahos
C J
CJ
Lilly Research Laboratories, Indianapolis, Indiana 46285.
Kriauciunas
T D
TD
Gleason
P E
PE
Jones
J A
JA
Eble
J N
JN
Salvas
D
D
Falcone
J F
JF
Hirsch
K S
KS
D000368:Aged; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011470:Prostatic Hyperplasia / Q000473:pathology*; D011499:Protein Processing, Post-Translational; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D013268:Stimulation, Chemical
D010982:Platelet-Derived Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017479:Receptors, Platelet-Derived Growth Factor