Coordinated expression of matrilysin during TPA-induced apoptosis of LNCaP cells: Two parallel processes affected by TPA

Padma Sundareshan, James J. Koster, Ray B. Nagle, G. Tim Bowden

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Matrix metalloproteinases (MMPs) are upregulated by growth factors and 12-O-tetradecandyl-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 μM, 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.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalCancer Letters
Volume113
Issue number1-2
DOIs
StatePublished - Feb 26 1997

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Keywords

  • Apoptosis
  • BB-2516
  • LNCaP human prostate carcinoma cell line
  • Matrilysin
  • TPA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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