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