TGF-β-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells

  • Authors:
    • Eun-Sook Kim
    • Mi-Sung Kim
    • Aree Moon
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/ijo.25.5.1375
  • Pages: 1375-1382
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Transforming growth factor (TGF)-β has been reported to exert growth inhibitory activity in normal epithelial cells whereas it induces cell proliferation and invasive phenotypes in advanced carcinomas. Our previous study showed that MCF10A, a spontaneously immortalized ‘normal’ breast epithelial cell line, is resistant to TGF-β-induced growth inhibition, suggesting that conversion of TGF-β growth inhibitory signaling into an oncogenic pathway may occur at the early stage of tumor development/progression. To address this issue, we investigated the TGF-β signaling pathway and its role in phenotypic transformation of MCF10A cells. TGF-β treatment induced changes in the MCF10A cell morphology from cuboidal to an elongated spindle-like shape, accompanied with down-regulation of epithelial cell marker E-cadherin. TGF-β treatment was sufficient to induce migrative and invasive phenotypes in these cells, an important phenotypic conversion during tumor progression. We also showed that TGF-β treatment rapidly activated ERK-1/2 and p38 MAPK leading to upregulation of matrix metalloproteinase (MMP)-2 and MMP-9. Using chemical inhibitors and dominant negative mutants of MAPKs, we provide evidence that while both p38 MAPK and ERKs are required for TGF-β-induced MCF10A cell migration and invasion, TGF-β-induced MMP-2 and MMP-9 expression depends on p38 MAPK signaling, but is independent of ERK activity. This study demonstrates the roles of TGF-β signaling pathways for induction of oncogenic signaling in preneoplastic human breast epithelial cells and will deepen our understanding of TGF-β signaling in the progress of breast cancer.

Related Articles

Journal Cover

November 2004
Volume 25 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kim E, Kim M and Moon A: TGF-β-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. Int J Oncol 25: 1375-1382, 2004.
APA
Kim, E., Kim, M., & Moon, A. (2004). TGF-β-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells. International Journal of Oncology, 25, 1375-1382. https://doi.org/10.3892/ijo.25.5.1375
MLA
Kim, E., Kim, M., Moon, A."TGF-β-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells". International Journal of Oncology 25.5 (2004): 1375-1382.
Chicago
Kim, E., Kim, M., Moon, A."TGF-β-induced upregulation of MMP-2 and MMP-9 depends on p38 MAPK, but not ERK signaling in MCF10A human breast epithelial cells". International Journal of Oncology 25, no. 5 (2004): 1375-1382. https://doi.org/10.3892/ijo.25.5.1375