title: Distribution of RANK and RANK Ligand in Normal Human Tissues as Determined by an Optimized Immunohistochemical Method.
abstract: The expression and tissue distribution of RANK (Receptor Activator of Nuclear Factor κ B) and RANK Ligand (RANKL) are of critical interest in relation to efficacy and safety of antibodies against RANK or RANKL that are approved or under consideration as potential therapeutic agents. Data from the literature using protein or mRNA analyses of rodent and human tissues or immunohistochemical (IHC) studies with a variety of antibodies and methods have provided some background of the distribution of RANK and RANKL but have yielded inconsistent findings. The present study reports the generation of carefully validated antibodies to RANK and RANKL and the development of an optimized IHC method, with confirmatory data from 2 well-validated alternative protocols that were developed and performed in separate laboratories at USC and at Amgen. Tissue expression of RANK and RANKL is reported for the optimized IHC assay.
authors.affiliation: *Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles ‡Dako, an Agilent technologies company, Carpinteria ∥Department of Comparative Biology and Safety Sciences ¶Formerly Department of Pathology, Amgen Inc., Thousand Oaks, CA †Formerly Department of Pathology §Department of Oncology Research, Amgen Inc., Seattle WA.
authors.forename: Clive R
authors.initials: CR
authors.lastname: Taylor
authors.forename: Daniel
authors.initials: D
authors.lastname: Branstetter
authors.forename: Edward
authors.initials: E
authors.lastname: Manna
authors.forename: William C
authors.initials: WC
authors.lastname: Dougall
authors.forename: Jeanine
authors.initials: J
authors.lastname: Bussiere
authors.forename: Carol W
authors.initials: CW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods* / Q000592:standards; D051379:Mice; D053245:RANK Ligand / Q000737:chemistry / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000737:chemistry / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D000906:Antibodies; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B