The enhancement by pervanadate of tyrosine phosphorylation on prostatic proteins occurs through the inhibition of membrane-associated tyrosine phosphatases.
The relapse of prostate cancer during endocrine therapies is attributed to the proliferation of growth factor (GF)-dependent epithelial cells. Such cells are present but in a quiescent state in the normal adult human and dog (experimental model) prostates. GF-signaling pathways involve the activation of protein tyrosine kinases (PTK) whose action is also modulated by phosphotyrosine protein phosphatases (PTPs). To that effect, we have previously reported that dividing canine prostatic epithelial cells exhibited high levels of phosphotyrosyl-(pY)-proteins which were greatly enhanced when incubated in the presence of vanadate. The aim of this study, performed with pervanadate (pV), was to determine whether pV acts either directly by stimulating prostatic PTKs or indirectly by inhibiting PTPs. Upon fractionation, most of the PTK activity was found in membranes of dividing cells and pV selectively increased its activity. This was due to an inhibition of intrinsic PTPs, as demonstrated by dephosphorylation of endogenous pY-proteins which was abolished by pV. This activity was very sensitive to pV (IC50: 150 nM) and was due to non-secreted forms of prostatic acid phosphatase (PAP), a pV inhibited-enzyme, as well as to PTP-1 B, as demonstrated by gel filtration, isoelectric focusing and probing with antibodies. These enzymes were also detected in membranes from human hyperplastic/neoplastic prostates but only PTP-1 B was present in those of prostatic carcinoma PC3 cells. These PTPs, bound to membranes of dividing cells (normal vs neoplastic) where activated PTKs are also located, may be of importance in the development and progression of prostatic proliferative diseases.
Boissonneault
M
M
Montreal General Hospital Research Institute, Canada.
Chapdelaine
A
A
Chevalier
S
S
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D004285:Dogs; D004848:Epithelium / Q000378:metabolism; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011467:Prostate / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism*; D014638:Vanadates / Q000494:pharmacology*
D011506:Proteins; D014638:Vanadates; D014443:Tyrosine; D017027:Protein Tyrosine Phosphatases