title: Correlation of serpin-protease expression by comparative analysis of real-time PCR profiling data.
abstract: Imbalanced protease activity has long been recognized in the progression of disease states such as cancer and inflammation. Serpins, the largest family of endogenous protease inhibitors, target a wide variety of serine and cysteine proteases and play a role in a number of physiological and pathological states. The expression profiles of 20 serpins and 105 serine and cysteine proteases were determined across a panel of normal and diseased human tissues. In general, expression of serpins was highly restricted in both normal and diseased tissues, suggesting defined physiological roles for these protease inhibitors. A high correlation in expression for a particular serpin-protease pair in healthy tissues was often predictive of a biological interaction. The most striking finding was the dramatic change observed in the regulation of expression between proteases and their cognate inhibitors in diseased tissues. The loss of regulated serpin-protease matched expression may underlie the imbalanced protease activity observed in pathological states.
authors.affiliation: Millennium Pharmaceuticals, Inc., 40 Landsdowne Street, Cambridge, MA 02139, USA.
authors.forename: Sunita
authors.initials: S
authors.lastname: Badola
authors.forename: Heidi
authors.initials: H
authors.lastname: Spurling
authors.forename: Keith
authors.initials: K
authors.lastname: Robison
authors.forename: Eric R
authors.initials: ER
authors.lastname: Fedyk
authors.forename: Gary A
authors.initials: GA
authors.lastname: Silverman
authors.forename: Jochen
authors.initials: J
authors.lastname: Strayle
authors.forename: Rosana
authors.initials: R
authors.lastname: Kapeller
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Tsu
mesh_terms: D000595:Amino Acid Sequence; D002460:Cell Line; D002461:Cell Line, Transformed; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods*; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D013045:Species Specificity
chemical_list: D015843:Serpins; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases