LEF-1 regulates proliferation and MMP-7 transcription in breast cancer cells.
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 D1 and a gene encoding MMP-7 in breast cancer cells. Thus, a decrease of LEF-1 expression using LEF-1 siRNA resulted in down-regulation of cyclin D and MMP-7 expression, respectively. Moreover, cell cycle analysis of LEF-1 siRNA-transfected human breast cancer cells revealed a significant arrest in G2/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.
Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover, Podbielskistraße 380, Hannover, D-30659, Germany. Bucan.Vesna@mh-hannover.de
Vesna
V
Bucan
Katharina
K
Mandel
Catharina
C
Bertram
Andrea
A
Lazaridis
Kerstin
K
Reimers
Tjoung-Won
TW
Park-Simon
Peter M
PM
Vogt
Ralf
R
Hass
D001483:Base Sequence; D001665:Binding Sites; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000235:genetics / Q000378:metabolism*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D014158:Transcription, Genetic
D051821:Lymphoid Enhancer-Binding Factor 1; D020783:Matrix Metalloproteinase 7