TY - JOUR
T1 - p73 Expression in Human Normal and Tumor Tissues
T2 - Loss of p73α Expression Is Associated with Tumor Progression in Bladder Cancer
AU - Puig, Pere
AU - Capodieci, Paola
AU - Drobnjak, Marija
AU - Verbel, David
AU - Prives, Carol
AU - Cordon-Cardo, Carlos
AU - Di Como, Charles J.
PY - 2003/11/15
Y1 - 2003/11/15
N2 - Purpose: To characterize the expression profile of p73 in human normal tissues by immunohistochemistry (IHC) and to analyze the correlation between p73 expression and bladder cancer progression. Experimental Design: CJDp73 was characterized for p73α detection in Western blot and IHC through its application to isoform-transfected 293 cells. Normal tissues were analyzed by IHC with the CJDp73 antiserum. Transitional cell carcinoma (TCC)-derived cell lines were subjected to reverse transcription-PCR and Western blot. TCC tissue microarrays were analyzed for p73α expression by IHC, and the results were statistically analyzed. Results: p73 immunostaining was nuclear and restricted to epithelial cells of certain organs such as squamous epithelium of the epidermis and transitional epithelium of the bladder. The expression was also observed in certain specialized glandular epithelia such as acinar cells of breast and parotid gland. Four of seven TCC-derived cell lines had low to undetectable p73α protein levels. We found undetectable or low p73α expression in 104 of 154 (68%) TCC cases, this phenotype being more frequently observed in invasive tumors when compared with superficial lesions. This association was statistically significant (P < 0.0001). We also observed a significant association between p53, p63, and p73α alterations with bladder cancer progression (P < 0.0001). Conclusions: p73α plays a tumor suppressor role in bladder cancer, and its inactivation occurs through an epigenetic mechanism, most probably involving protein degradation.
AB - Purpose: To characterize the expression profile of p73 in human normal tissues by immunohistochemistry (IHC) and to analyze the correlation between p73 expression and bladder cancer progression. Experimental Design: CJDp73 was characterized for p73α detection in Western blot and IHC through its application to isoform-transfected 293 cells. Normal tissues were analyzed by IHC with the CJDp73 antiserum. Transitional cell carcinoma (TCC)-derived cell lines were subjected to reverse transcription-PCR and Western blot. TCC tissue microarrays were analyzed for p73α expression by IHC, and the results were statistically analyzed. Results: p73 immunostaining was nuclear and restricted to epithelial cells of certain organs such as squamous epithelium of the epidermis and transitional epithelium of the bladder. The expression was also observed in certain specialized glandular epithelia such as acinar cells of breast and parotid gland. Four of seven TCC-derived cell lines had low to undetectable p73α protein levels. We found undetectable or low p73α expression in 104 of 154 (68%) TCC cases, this phenotype being more frequently observed in invasive tumors when compared with superficial lesions. This association was statistically significant (P < 0.0001). We also observed a significant association between p53, p63, and p73α alterations with bladder cancer progression (P < 0.0001). Conclusions: p73α plays a tumor suppressor role in bladder cancer, and its inactivation occurs through an epigenetic mechanism, most probably involving protein degradation.
UR - http://www.scopus.com/inward/record.url?scp=0344326931&partnerID=8YFLogxK
M3 - Article
C2 - 14654547
AN - SCOPUS:0344326931
SN - 1078-0432
VL - 9
SP - 5642
EP - 5651
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 15
ER -