Transcriptional activation of collagenase-3 by transforming growth factor-beta1 is via MAPK and Smad pathways in human breast cancer cells

FEBS Lett. 2002 Dec 4;532(1-2):31-5. doi: 10.1016/s0014-5793(02)03620-7.

Abstract

Transforming growth factor (TGF)-beta1, a crucial molecule in metastatic bone cancer, stimulates collagenase-3 expression in the human breast cancer cell line, MDA-MB231. Cycloheximide inhibited this stimulation, indicating that de novo protein synthesis was essential for this response. We examined whether mitogen-activated protein kinase (MAPK) and/or Smad pathways are involved in TGF-beta1-stimulated collagenase-3 expression in MDA-MB231 cells. Biochemical blockade of extracellular regulated kinase-1/2 and p38 MAPK pathways partially abolished TGF-beta1-stimulated collagenase-3 mRNA expression; whereas overexpression of a dominant negative form of Smad3 completely blocked the TGF-beta1-response. These data indicate that TGF-beta1-induced MAPK and Smad pathways are involved in TGF-beta1-stimulated collagenase-3 expression in MDA-MB231 cells.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / metabolism
  • Collagenases / biosynthesis
  • Collagenases / genetics*
  • DNA-Binding Proteins / physiology*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Kinetics
  • MAP Kinase Signaling System / drug effects
  • Matrix Metalloproteinase 13
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / physiology*
  • Promoter Regions, Genetic
  • RNA, Messenger / biosynthesis
  • Signal Transduction
  • Smad Proteins
  • Trans-Activators / physiology*
  • Transcriptional Activation
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta1
  • Tumor Cells, Cultured
  • p38 Mitogen-Activated Protein Kinases

Substances

  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • RNA, Messenger
  • Smad Proteins
  • TGFB1 protein, human
  • Trans-Activators
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Collagenases
  • MMP13 protein, human
  • Matrix Metalloproteinase 13