Novel p53/p130 axis in bladder tumors.
OBJECTIVE
To identify the relationships between key components of the proliferative and apoptotic pathways in bladder tumors.


METHODS
A tissue array of 88 bladder tumors was assembled. Immunohistochemical analyses were used to investigate the relationship between nine different parameters: stage, proliferation (Ki67), apoptosis (in situ DNA nick end labeling), the anti-apoptotic protein Bcl-2, tumor suppressors p53 and retinoblastoma protein (Rb), the Rb-related protein p130, cyclin E, and the cyclin-dependent kinase inhibitor p27. The protein expression in each tumor was reported as the percentage of positively staining cells.


RESULTS
The analysis focused on Stage 1 to 3 tumors. Analysis found that p53 expression increased progressively with stage, and Rb and p27 decreased with increasing stage. Overall, the cyclin E levels correlated with the proliferative index. Cyclin E levels were low in Stage 1 tumors and elevated in Stage 2 tumors, but were decreased in Stage 3 tumors. Multivariate analysis uncovered a correlation between cyclin E and proliferation (Ki67) and a weak correlation between p53 and Bcl-2 and between p27 and Rb. A strong correlation was found between the expression of p53 and p130, which was apparent in Stages 1 and 3, but not in Stage 2. Furthermore, high levels of p130 protein were detected primarily in the cytoplasm.


CONCLUSIONS
These results suggest a novel p53/p130 axis in bladder tumors.
Mudryj
Maria
M
Veterans Affairs Northern California Health Care System, Mather, California, USA. mmudryj@ucdavis.edu
Reay
Elizabeth
E
Beckett
Laurel
L
Dandekar
Satya
S
deVere White
Ralph
R
Gandour-Edwards
Regina
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division; D002467:Cell Nucleus / Q000737:chemistry; D019927:Cyclin E / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D003593:Cytoplasm / Q000737:chemistry; D005260:Female; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000502:physiology*; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D050717:Retinoblastoma-Like Protein p130 / Q000032:analysis / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000473:pathology*
D019927:Cyclin E; D019394:Ki-67 Antigen; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C493837:RBL2 protein, human; D050717:Retinoblastoma-Like Protein p130; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27