Sp1 regulates cathepsin B transcription and invasiveness in murine B16 melanoma cells.
BACKGROUND
Increased expression of cathepsin B contributes to extracellular matrix degradation and invasion in cancer. Cathepsin B expression is under transcriptional control in murine melanomas and the major promoter contains potential binding sites for the Sp1 transcription factor.


METHODS
Murine melanoma cells transfected with an Sp1 expression plasmid or its control were used in Matrigel invasion and cell motility assays in the presence or absence of the cathepsin B inhibitor, CA-074Me.


RESULTS
Transfection of B16F1 cells with the Sp1 expression plasmid resulted in a 2.5- to 5.3 -fold increase in cathepsin B specific activity and a 4.8- to 5.5-fold increase in invasiveness over the control, but had no effect on the movement of cells across an uncoated membrane. CA-074Me treatment resulted in significantly reduced Matrigel invasion without affecting cell motility.


CONCLUSIONS
Sp1 can regulate the capacity of B16F1 cells to degrade a reconstituted extracellular matrix in part by regulating cathepsin B expression.
Szpaderska
Anna M
AM
Division of Molecular and Cellular Biochemistry, Department of Cell Biology, Neurobiology and Anatomy, Loyola University Medical Center, Maywood, IL 60153, USA.
Silberman
Simone
S
Ahmed
Yasmin
Y
Frankfater
Allen
A
D000818:Animals; D001485:Basement Membrane / Q000473:pathology; D002401:Cathepsin B / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D003094:Collagen; D004338:Drug Combinations; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D007797:Laminin; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D016329:Sp1 Transcription Factor / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D016329:Sp1 Transcription Factor; C059485:matrigel; D003094:Collagen; D002401:Cathepsin B