Coordinated expression of matrilysin during TPA-induced apoptosis of LNCaP cells: two parallel processes affected by TPA.
Matrix metalloproteinases (MMPs) are upregulated by growth factors and 12-O-tetradecanoyl-phorbol-13-acetate (TPA). TPA (10 nM) induced apoptosis in LNCaP cells grown in serum-free medium at high seeding density, and increased mRNA and secreted protein levels for the MMP matrilysin. While the TPA-augmented increase in matrilysin mRNA was seen at 4 h, secreted matrilysin protein levels at 8 h, TPA-induced DNA ladder formation was seen only at 10 h and the TPA-induced apoptosis was detected at 12 h. The sequence of events suggested a functional role for matrilysin in apoptosis. However, when the MMP inhibitor BB-2516 was used (25 microM, with IC50 of 20 nM for matrilysin), there was no effect of BB-2516 on TPA-induced apoptosis in LNCaP cells (P = 0.2072). This observation indicates that MMPs including matrilysin do not play a primary role in TPA-induced apoptosis in LNCaP cells. We conclude that the TPA-induced apoptosis and the regulation of matrilysin (a TPA-response element (TRE)-containing gene), are independent and parallel processes.
Sundareshan
P
P
Department of Radiation Oncology, Arizona Cancer Center, University of Arizona, Tucson 85724, USA.
Koster
J J
JJ
Nagle
R B
RB
Bowden
G T
GT
D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology*; D002452:Cell Count; D016895:Culture Media, Serum-Free; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D020783:Matrix Metalloproteinase 7; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013997:Time Factors; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D016895:Culture Media, Serum-Free; D012333:RNA, Messenger; D008666:Metalloendopeptidases; D020783:Matrix Metalloproteinase 7; D013755:Tetradecanoylphorbol Acetate