A-FABP, a candidate progression marker of human transitional cell carcinoma of the bladder, is differentially regulated by PPAR in urothelial cancer cells.
Superficial pT1 bladder tumors are characterized by a high risk of recurrence and progression in grade and stage. Few studies provided evidence that loss of adipocyte-fatty acid binding protein (A-FABP) expression was associated with bladder cancer progression. A-FABP is a lipid binding protein playing a role in intracellular lipid transport and metabolism, as well as in signal transduction. We reported from bladder tumors that decrease of A-FABP transcript level significantly correlated to tumor stage and to histologic grade (p < 0.05). Namely, in poor prognosis high grade pT1 tumors there was a loss of A-FABP expression compared to good prognosis tumors suggesting that re-expression of A-FABP could be a therapeutic approach in early stage bladder cancer to prevent disease progression. We demonstrated for the first time that this marker is upregulated by Peroxisome Proliferator-Activated Receptor (PPAR) alpha, beta and gamma in T24 cells (derived from an undifferentiated grade III carcinoma) and only by PPARbeta in RT4 cells (derived from a well differentiated grade I papillary tumor). This effect occurred through a PPAR-dependent transcriptional mechanism without modifying mRNA stability and interestingly required de novo protein synthesis. Data as a whole suggest a prognostic significance of A-FABP in bladder cancer outcome and the potential utility of overexpression of this protein by PPAR agonists open up new perspectives in the treatment of bladder cancer. (c) 2008 Wiley-Liss, Inc.
Boiteux
Guillaume
G
Laboratoire de Biologie Cellulaire et Moléculaire, EA 3181-IBCT-IFR No. 133, Université de Franche-Comté, UFR des Sciences Médicales et Pharmaceutiques, Besançon Cedex 3, France.
Lascombe
Isabelle
I
Roche
Emmanuelle
E
Plissonnier
Marie-Laure
ML
Clairotte
Anne
A
Bittard
Hugues
H
Fauconnet
Sylvie
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism*; D018450:Disease Progression; D050556:Fatty Acid-Binding Proteins / Q000096:biosynthesis* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D015398:Signal Transduction; D001749:Urinary Bladder Neoplasms / Q000378:metabolism*; D019459:Urothelium / Q000378:metabolism*
D014408:Biomarkers, Tumor; C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins; D047492:Peroxisome Proliferator-Activated Receptors