Expression of the protein phosphatase 1 inhibitor KEPI is downregulated in breast cancer cell lines and tissues and involved in the regulation of the tumor suppressor EGR1 via the MEK-ERK pathway

Katrin Wenzel; Katjana Daskalow; Florian Herse; Susanne Seitz; Ute Zacharias; Jörg A Schenk; Herbert Schulz; Norbert Hubner; Burkhard Micheel; Peter M Schlag; Karl J Osterziel; Cemil Ozcelik; Siegfried Scherneck; Burkhard Jandrig

doi:10.1515/BC.2007.062

Expression of the protein phosphatase 1 inhibitor KEPI is downregulated in breast cancer cell lines and tissues and involved in the regulation of the tumor suppressor EGR1 via the MEK-ERK pathway

Biol Chem. 2007 May;388(5):489-95. doi: 10.1515/BC.2007.062.

Authors

Katrin Wenzel¹, Katjana Daskalow, Florian Herse, Susanne Seitz, Ute Zacharias, Jörg A Schenk, Herbert Schulz, Norbert Hubner, Burkhard Micheel, Peter M Schlag, Karl J Osterziel, Cemil Ozcelik, Siegfried Scherneck, Burkhard Jandrig

Affiliation

¹ Max Delbrück Center for Molecular Medicine, Robert-Rössle-Strasse 10, Berlin, Germany. kwenzel@mdc-berlin.de

PMID: 17516844
DOI: 10.1515/BC.2007.062

Abstract

KEPI is a protein kinase C-potentiated inhibitory protein for type 1 Ser/Thr protein phosphatases. We found no or reduced expression of KEPI in breast cancer cell lines, breast tumors and metastases in comparison to normal breast cell lines and tissues, respectively. KEPI protein expression and ubiquitous localization was detected with a newly generated antibody. Ectopic KEPI expression in MCF7 breast cancer cells induced differential expression of 95 genes, including the up-regulation of the tumor suppressors EGR1 (early growth response 1) and PTEN (phosphatase and tensin homolog), which is regulated by EGR1. We further show that the up-regulation of EGR1 in MCF7/KEPI cells is mediated by MEK-ERK signaling. The inhibition of this pathway by the MEK inhibitor UO126 led to a strong decrease in EGR1 expression in MCF7/KEPI cells. These results reveal a novel role for KEPI in the regulation of the tumor suppressor gene EGR1 via activation of the MEK-ERK MAPK pathway.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / genetics
Breast Neoplasms / metabolism*
Breast Neoplasms / pathology
Cell Line, Tumor
Down-Regulation*
Early Growth Response Protein 1 / metabolism*
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / metabolism*
Gene Expression Regulation, Neoplastic
Humans
Intracellular Signaling Peptides and Proteins
MAP Kinase Signaling System*
Mitogen-Activated Protein Kinase Kinases / metabolism*
Neoplasm Metastasis
PTEN Phosphohydrolase / genetics
PTEN Phosphohydrolase / metabolism
Phosphoprotein Phosphatases / genetics
Phosphoprotein Phosphatases / metabolism*
Protein Phosphatase 1
RNA, Messenger
Tumor Suppressor Proteins / metabolism
Up-Regulation

Substances

EGR1 protein, human
Early Growth Response Protein 1
Intracellular Signaling Peptides and Proteins
PPP1R14C protein, human
RNA, Messenger
Tumor Suppressor Proteins
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase Kinases
Phosphoprotein Phosphatases
Protein Phosphatase 1
PTEN Phosphohydrolase
PTEN protein, human