title: Posttranslational truncation and inactivation of human E-cadherin distinguishes prostate cancer from matched normal prostate.
abstract: An essential event in the progression of adenocarcinoma is the loss of organized epithelial attachment (both to the basement membrane and to adjoining epithelial cells). The E-cadherin cell adhesion molecule has an established function in maintaining normal phenotype and tissue homeostasis, and loss of E-cadherin function has been implicated in tumorigenesis. Aberrations in E-cadherin are associated with prostate cancer progression; however, these aberrations are not simply a result of prodigious allelic loss. We have previously demonstrated a novel posttranslational truncation within the cytosolic domain of native Mr 120,000 E-cadherin to a membrane-bound Mr 97,000 species. We hypothesize that truncation of E-cadherin is an inactivating event that is significantly increased in localized prostate tumors and that it represents a novel molecular event that may distinguish prostate cancer from adjacent normal tissue. E-cadherin was characterized by Western blot analysis in matched normal and cancer tissue from 18 prostate cancer patients. Imaging and densitometry software were used to quantify the truncation of E-cadherin by measuring the ratio of Mr 97,000 E-cadherin to Mr 120,000 E-cadherin, which was significantly increased in the tumor aspect of the prostate gland. Herein, we report the first experiment comparing case-matched human normal and cancerous prostate tissue in the context of E-cadherin truncation.
authors.affiliation: Department of Surgery, and the University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109-0944, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Rashid
authors.forename: M G
authors.initials: MG
authors.lastname: Sanda
authors.forename: C J
authors.initials: CJ
authors.lastname: Vallorosi
authors.forename: J
authors.initials: J
authors.lastname: Rios-Doria
authors.forename: M A
authors.initials: MA
authors.lastname: Rubin
authors.forename: M L
authors.initials: ML
authors.lastname: Day
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008970:Molecular Weight; D011233:Precipitin Tests; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational
chemical_list: D015820:Cadherins