Protein tyrosine phosphatase controls breast cancer invasion through the expression of matrix metalloproteinase-9.

Abstract

The expression of matrix metalloproteinases (MMPs) produced by cancer cells has been associated with the high potential of metastasis in several human carcinomas, including breast cancer. Several pieces of evidence demonstrate that protein tyrosine phosphatases (PTP) have functions that promote cell migration and metastasis in breast cancer. We analyzed whether PTP inhibitor might control breast cancer invasion through MMP expression. Herein, we investigate the effect of 4-hydroxy-3,3-dimethyl-2H benzo[g]indole-2,5(3H)-dione (BVT948), a novel PTP inhibitor, on 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion in MCF-7 cells. The expression of MMP-9 and cell invasion increased after TPA treatment, whereas TPA-induced MMP-9 expression and cell invasion were decreased by BVT948 pretreatment. Also, BVT948 suppressed NF-κB activation in TPA-treated MCF-7 cells. However, BVT948 didn't block TPA-induced AP-1 activation in MCF-7 cells. Our results suggest that the PTP inhibitor blocks breast cancer invasion via suppression of the expression of MMP-9.

• Authors: Bo-Mi Hwang, Hee Suk Chae, Young-Ju Jeong, Young-Rae Lee, Eun-Mi Noh, Hyun Zo Youn, Sung Hoo Jung, Hong-Nu Yu, Eun Yong Chung, Jong-Suk Kim
• Journal: BMB reports (BMB Rep) Vol. 46 Issue 11 Pg. 533-8 (Nov 2013) ISSN: 1976-670X [Electronic] Korea (South)
• PMID: 24152909 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 4-hydroxy-3,3-dimethyl-2H-benzo(g)indole-2,5(3H)-dione
• Carcinogens
• Indoles
• NF-kappa B
• Transcription Factor AP-1
• Mitogen-Activated Protein Kinases
• Protein Tyrosine Phosphatases
• Matrix Metalloproteinase 9
• Tetradecanoylphorbol Acetate

Topics

• Breast Neoplasms (enzymology, metabolism, pathology)
• Carcinogens (pharmacology)
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Female
• Gene Expression Regulation, Enzymologic (drug effects)
• Humans
• Indoles (pharmacology)
• MCF-7 Cells
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Protein Tyrosine Phosphatases (antagonists & inhibitors, metabolism)
• Tetradecanoylphorbol Acetate (pharmacology)
• Transcription Factor AP-1 (metabolism)