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Transcriptional activation of collagenase‐3 by transforming growth factor‐β1 is via MAPK and Smad pathways in human breast cancer cells
Author(s) -
Selvamurugan Nagarajan,
Fung Ziawei,
Partridge Nicola C
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03620-7
Subject(s) - smad , mapk/erk pathway , collagenase , transforming growth factor , cycloheximide , signal transduction , protein kinase a , cancer research , kinase , biology , microbiology and biotechnology , chemistry , endocrinology , medicine , protein biosynthesis , biochemistry , enzyme
Transforming growth factor (TGF)‐β1, 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‐β1‐stimulated collagenase‐3 expression in MDA‐MB231 cells. Biochemical blockade of extracellular regulated kinase‐1/2 and p38 MAPK pathways partially abolished TGF‐β1‐stimulated collagenase‐3 mRNA expression; whereas overexpression of a dominant negative form of Smad3 completely blocked the TGF‐β1‐response. These data indicate that TGF‐β1‐induced MAPK and Smad pathways are involved in TGF‐β1‐stimulated collagenase‐3 expression in MDA‐MB231 cells.