Calcitriol inhibits growth response to Platelet-Derived Growth Factor-BB in human prostate cells.
Calcitriol, a hormonal form of Vitamin D, regulates growth of normal and cancer cells of various origins by modulation of peptide growth factors signaling. Platelet-Derived Growth Factor (PDGF) signaling pathway is involved in prostate cancer progression. We studied the expression of PDGF receptors in human prostate primary stromal cells and cancer epithelial cell lines and growth response to PDGF-BB isoform. We found that the expression of PDGF receptors and PDGF-BB-mediated cell growth are regulated by calcitriol in prostate cells. Quantitative RT-PCR analysis revealed a lower level of mRNA for PDGF receptors in LNCaP and PC-3 cells than in primary stromal cells. Western blotting showed a high amount of PDGFRalpha and beta proteins in primary stromal cells that could not be detected in LNCaP, which may explain the resistance of LNCaP cells to growth-promoting effect of PDGF-BB. Addition of Epidermal Growth Factor (EGF) to the culture medium induces the expression of PDGFRbeta and restores responsiveness of LNCaP to PDGF-BB to some extent. Calcitriol down-regulates PDGFRbeta expression and negatively regulates PDGF-mediated cell growth. Calcitriol does not affect PDGFRalpha and PDGF-B mRNA expression. We suggest that inhibition of PDGFRbeta expression by calcitriol might reduce responsiveness of prostate cells to mitogenic action of PDGF-BB.
Nazarova
Nadja
N
Department of Anatomy, Medical School, University of Tampere, 33014 Tampere, Finland. nadya.nazarova@uta.fi
Golovko
Olga
O
Bläuer
Merja
M
Tuohimaa
Pentti
P
D001483:Base Sequence; D000077214:Becaplermin; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D017931:DNA Primers; D006801:Humans; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011467:Prostate / Q000187:drug effects / Q000502:physiology*; D011471:Prostatic Neoplasms; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000187:drug effects / Q000235:genetics*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000502:physiology
D017931:DNA Primers; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D000077214:Becaplermin; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D002117:Calcitriol