Transcriptional repression of MMP-1 by p21SNFT and reduced in vitro invasiveness of hepatocarcinoma cells.
p21SNFT (21 kDa small nuclear factor isolated from T cells) is a human basic leucine zipper transcription factor that can repress AP-1-mediated transcription. We show here that overexpression of p21SNFT in HepG2 cells leads to repression of matrix metalloproteinase-1 by 70-80%. p21SNFT interacted with Jun at the matrix metalloproteinase-1 promoter -88 Ets/AP-1 enhancer element, where Jun is known to activate transcription via interaction with Fos and Ets proteins. When p21SNFT/Jun dimers bound the element in the presence of Ets, DNA was protected differently than when Fos was paired with Jun. The data suggest a difference in overall conformation between p21SNFT-containing and Fos-containing complexes that may be involved in the repression of matrix metalloproteinase-1 by p21SNFT. Overexpression of p21SNFT led to a reduction in invasiveness of HepG2 cells through type I collagen and reconstituted basement membrane, an effect similar to that obtained via direct immunodepletion of matrix metalloproteinase-1. The results indicate that the mechanism of repression of matrix metalloproteinase-1 by p21SNFT may be exploited in inhibiting pathological matrix remodeling during cancer progression in vivo.
Bower
Kristen E
KE
Department of Biology, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182-4614, USA. kbower@scripps.edu
Fritz
Jamie M
JM
McGuire
Kathleen L
KL
D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D003094:Collagen / Q000502:physiology; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D004742:Enhancer Elements, Genetic; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
C411483:BATF3 protein, human; D050976:Basic-Leucine Zipper Transcription Factors; D017931:DNA Primers; D012097:Repressor Proteins; D014157:Transcription Factors; D003094:Collagen; D020781:Matrix Metalloproteinase 1