Gene expression study of Aurora-A reveals implication during bladder carcinogenesis and increasing values in invasive urothelial cancer.
OBJECTIVE
Urothelial carcinoma is a frequent and aggressive cancer. We wanted to gain better insight into the early molecular mechanisms of bladder carcinogenesis by evaluating Aurora-A gene expression, which is implicated in genomic stability and essential for mitosis.


METHODS
This study, using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), analyzed the expression levels of three selected genes in dissected tissues from normal bladder, noninvasive cancers, and muscle-invasive bladder carcinomas (n = 49). We compared gene expression levels of three genes (Aurora-A, and as control uroplakin II (UPII) and TBP, respectively) at different stages of bladder cancer. We used multivariate analysis, receiver operating characteristic curves and the nonparametric Mann-Whitney test.


RESULTS
The expression of Aurora-A gene studied was significantly deregulated, with an increasing level in cancer versus normal tissue Aurora-A. This development was linear. Aurora-A was already deregulated in early stages of carcinogenesis (pTa/pT1) (P = 0.0004) and displayed even more deregulation in muscle-invasive stages (pT2 to pT4). Immunohistochemistry performed on the same samples using Aurora-A antibody confirmed results of RT-PCR, with statistically significant values when comparing m-RNA expression and immunohistochemical values (P = 0.0001).


CONCLUSIONS
This study highlights the fact that Aurora-A gene expression is already strongly deregulated in early stages of urothelial carcinoma with abnormal expression, and might be considered a biomarker of tumor aggression. The increase in Aurora-A expression might provide further information regarding the behavior of bladder cancer in daily practice.
Compérat
Eva
E
CNRS UMR 8149, Faculté de Pharmacie, Paris V, Paris, France. evacomperat@yahoo.fr
Bièche
Ivan
I
Dargère
Delphine
D
Laurendeau
Ingrid
I
Vieillefond
Annick
A
Benoit
Gérard
G
Vidaud
Michel
M
Camparo
Philippe
P
Capron
Fréderique
F
Verret
Catherine
C
Cussenot
Olivier
O
Bedossa
Pierre
P
Paradis
Valérie
V
D000368:Aged; D000369:Aged, 80 and over; D064127:Aurora Kinases; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*; D019459:Urothelium / Q000473:pathology
D012333:RNA, Messenger; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases