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LEF ‐1 regulates proliferation and MMP ‐7 transcription in breast cancer cells
Author(s) -
Bucan Vesna,
Mandel Katharina,
Bertram Catharina,
Lazaridis Andrea,
Reimers Kerstin,
ParkSimon TjoungWon,
Vogt Peter M.,
Hass Ralf
Publication year - 2012
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2012.01613.x
Subject(s) - biology , cyclin d1 , enhancer , cancer research , transcription factor , microbiology and biotechnology , promoter , transfection , breast cancer , cell cycle , gene , cancer , gene expression , genetics
Matrix metalloproteinase‐7 ( MMP ‐7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression is associated with tumor invasion, metastasis, and survival in a variety of cancers including breast cancer. Using bioinformatics analysis, a conserved LEF ‐1 binding site became obvious that is mapped at the promoter region of the genomic MMP ‐7 locus. Consequently, electrophoretic mobility shift assay demonstrated in vitro binding of LEF ‐1 to the predicted MMP ‐7 promoter binding site. Here, we demonstrate that lymphoid enhancer binding factor‐1 ( LEF ‐1) is associated with regulation of the proliferation‐associated cyclin D 1 and a gene encoding MMP ‐7 in breast cancer cells. Thus, a decrease of LEF ‐1 expression using LEF ‐1 si RNA resulted in down‐regulation of cyclin D and MMP ‐7 expression, respectively. Moreover, cell cycle analysis of LEF ‐1 si RNA ‐transfected human breast cancer cells revealed a significant arrest in G 2 / M phase. Taken together, our results indicate a pivotal role of LEF ‐1 in the regulation of proliferation and MMP ‐7 transcription in breast cancer cells.