title: A disintegrin and metalloproteinase-12 (ADAM12): function, roles in disease progression, and clinical implications.
abstract: BACKGROUND
  A disintegrin and metalloproteinase-12 (ADAM12) is a member of the greater ADAM family of enzymes: these are multifunctional, generally membrane-bound, zinc proteases for which there are forty genes known (21 of these appearing in humans). ADAM12 has been implicated in the pathogenesis of various cancers, liver fibrogenesis, hypertension, and asthma, and its elevation or decrease in human serum has been linked to these and other physiological/pathological conditions.
  
  
  METHODS
  In this review, we begin with a brief overview of the ADAM family of enzymes and protein structure. We then discuss the role of ADAM12 in the progression and/or diagnosis of various disease conditions, and we will conclude with an exploration of currently known natural and synthetic inhibitors.
  
  
  CONCLUSIONS
  ADAM12 has potential to emerge as a successful drug target, although targeting the metalloproteinase domain with any specificity will be difficult to achieve due to structural similarity between the members of the ADAM and MMP family of enzymes. Overall, more research is required to establish ADAM12 being as a highly desirable biomarker and drug target of different diseases, and their selective inhibitors as potential therapeutic agents.
  
  
  CONCLUSIONS
  Given the appearance of elevated levels of ADAM12 in various diseases, particularly breast cancer, our understanding of this enzyme both as a biomarker and a potential drug target could help make significant inroads into both early diagnosis and treatment of disease.
authors.affiliation: Department of Pharmaceutical Sciences, North Dakota State University, Fargo, ND 58108-6050, USA.
authors.forename: Erin K
authors.initials: EK
authors.lastname: Nyren-Erickson
authors.forename: Justin M
authors.initials: JM
authors.lastname: Jones
authors.forename: D K
authors.initials: DK
authors.lastname: Srivastava
authors.forename: Sanku
authors.initials: S
authors.lastname: Mallik
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D000072199:ADAM12 Protein; D055162:Biocatalysis; D004194:Disease / Q000145:classification; D018450:Disease Progression; D018734:Genes, erbB-2; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology*; D008958:Models, Molecular
chemical_list: D008565:Membrane Proteins; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human
keywords: ADAM12; Disintegrin and metalloproteinase; Function; Inhibitors; Structure