JOURNAL ARTICLE

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

Nagarajan Selvamurugan, Ziawei Fung, Nicola C Partridge
FEBS Letters 2002 December 4, 532 (1-2): 31-5
12459458
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.

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