Posttranslational truncation and inactivation of human E-cadherin distinguishes prostate cancer from matched normal prostate.
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.
Rashid
M G
MG
Department of Surgery, and the University of Michigan Comprehensive Cancer Center, University of Michigan, Ann Arbor 48109-0944, USA.
Sanda
M G
MG
Vallorosi
C J
CJ
Rios-Doria
J
J
Rubin
M A
MA
Day
M L
ML
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
D015820:Cadherins