p63 gene expression study and early bladder carcinogenesis.
OBJECTIVE
Urothelial carcinoma is a frequent and aggressive cancer. To gain better insight into the early molecular mechanisms of bladder carcinogenesis, this study analyzed the expression levels of four selected genes (uroplakin II, TATA-BOX-binding protein (TBP/RNA) control gene (NM_00394), and the two main isoforms TATp63 and deltaNp63 of p63).


METHODS
We used real-time quantitative reverse transcriptase-polymerase chain reaction in dissected tissues from normal bladder, noninvasive cancer, and muscle-invasive bladder carcinoma (n = 49). The gene expression levels were compared at different stages of bladder cancer. To confirm the results on protein levels, we used immunohistochemistry on tissue microarrays of the same samples.


RESULTS
The expression of the p63 gene studied was significantly deregulated, with decreasing levels in early cancer versus normal tissue. Immunohistochemistry, performed on the same samples, using p63 antibody, confirmed the results of reverse transcriptase-polymerase chain reaction.


CONCLUSIONS
The results of this study highlight that among the genes strongly deregulated in urothelial carcinoma, p63 is already abnormally expressed in the early stages.
Compérat
Eva
E
CNRS UMR 8149, Faculté de Pharmacie Paris V, Paris, France. evacomperat@yahoo.fr
Bièche
Ivan
I
Dargère
Delphine
D
Ferlicot
Sophie
S
Laurendeau
Ingrid
I
Benoît
Gérard
G
Vieillefond
Annick
A
Verret
Catherine
C
Vidaud
Michel
M
Capron
Fréderique
F
Bedossa
Pierre
P
Paradis
Valérie
V
D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D035181:TATA-Box Binding Protein / Q000096:biosynthesis / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060170:Uroplakin II
D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D035181:TATA-Box Binding Protein; C115051:TP63 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C554658:UPK2 protein, human; D060170:Uroplakin II