title: Serum antibodies to huntingtin interacting protein-1: a new blood test for prostate cancer.
abstract: Huntingtin-interacting protein 1 (HIP1) is frequently overexpressed in prostate cancer. HIP1 is a clathrin-binding protein involved in growth factor receptor trafficking that transforms fibroblasts by prolonging the half-life of growth factor receptors. In addition to human cancers, HIP1 is also overexpressed in prostate tumors from the transgenic adenocarcinoma of the mouse prostate (TRAMP) mouse model. Here we provide evidence that HIP1 plays an important role in mouse tumor development, as tumor formation in the TRAMP mice was impaired in the Hip1null/null background. In addition, we report that autoantibodies to HIP1 developed in the sera of TRAMP mice with prostate cancer as well as in the sera from human prostate cancer patients. This led to the development of an anti-HIP1 serum test in humans that had a similar sensitivity and specificity to the anti-alpha-methylacyl CoA racemase (AMACR) and prostate-specific antigen tests for prostate cancer and when combined with the anti-AMACR test yielded a specificity of 97%. These data suggest that HIP1 plays a functional role in tumorigenesis and that a positive HIP1 autoantibody test may be an important serum marker of prostate cancer.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109-0942, USA.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Bradley
authors.forename: Katherine I
authors.initials: KI
authors.lastname: Oravecz-Wilson
authors.forename: Gaelle
authors.initials: G
authors.lastname: Bougeard
authors.forename: Ikuko
authors.initials: I
authors.lastname: Mizukami
authors.forename: Lina
authors.initials: L
authors.lastname: Li
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Munaco
authors.forename: Arun
authors.initials: A
authors.lastname: Sreekumar
authors.forename: Michael N
authors.initials: MN
authors.lastname: Corradetti
authors.forename: Arul M
authors.initials: AM
authors.lastname: Chinnaiyan
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sanda
authors.forename: Theodora S
authors.initials: TS
authors.lastname: Ross
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human