Regulation of matrix metalloproteinase 13 expression by androgen in prostate cancer

Oncol Rep. 2004 Jun;11(6):1187-92.

Abstract

The matrix metalloproteinases (MMPs) are members of a family of endopeptidases that are able to degrade extra-cellular matrix. MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), play a key role in the migration of normal and malignant cell. Interaction of MMPs and TIMPs has been involved in the process of tumor invasion and metastasis. Using cDNA microarray as a screening tool to find androgen regulated gene in prostate cancer, we have found that expression of MMP-13 is regulated by androgen in prostate cancer derived cell line LNCaP. This regulation was further confirmed and quantified by real-time RT-PCR. In addition, the upregulation of MMP-13 mRNA by androgen could be abolished by the androgen antagonist Casodex but not the protein inhibitor cycloheximide. Western blot and immunohistochemistry of MMP-13 confirmed the androgen regulation at the protein level. We have furthermore shown that MMP-13 expression is presented in human prostate cancer obtained from aspiration biopsy. In summary, MMP-13 is androgen regulated and detectable in prostate cancer. Further study of MMP-13 in prostate cancer may help us to understand the progression of the cancer and can lead to new therapeutic options.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology
  • Androgens / pharmacology*
  • Anilides / pharmacology
  • Collagenases / genetics*
  • Collagenases / metabolism*
  • Cycloheximide / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Matrix Metalloproteinase 13
  • Nitriles
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / enzymology*
  • Prostatic Neoplasms / pathology
  • Protein Synthesis Inhibitors / pharmacology
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tosyl Compounds
  • Tumor Cells, Cultured

Substances

  • Androgen Antagonists
  • Androgens
  • Anilides
  • Nitriles
  • Protein Synthesis Inhibitors
  • RNA, Messenger
  • Tosyl Compounds
  • Cycloheximide
  • bicalutamide
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13