TY - JOUR
T1 - Progressive loss of CD44 gene expression in invasive bladder cancer
AU - Sugino, Takashi
AU - Gorham, Hazel
AU - Yoshida, Kazuhiro
AU - Bolodeoku, John
AU - Nargund, Vinod
AU - Cranston, David
AU - Goodison, Steve
AU - Tarin, David
PY - 1996/9
Y1 - 1996/9
N2 - This study investigated CD44 gene expression at both the RNA and protein level in well differentiated superficial and in deeply invasive bladder carcinomas. Proteins were studied by immunohistochemistry using antibodies against standard (CD44s) and variant (CD44v) isoforms. mRNA was analyzed by reverse transcriptase polymerase chain reaction/Southern blotting and in situ hybridization. Immunostaining with antibodies against CD44s and CD44v2, -5 and -6 (exons 7, 10, and 11, respectively) showed that carcinoma cells in all papillary tumors expressed strong signals throughout the epithelium but especially in the basal layer, which abuts on the stroma. However, invasive tumors, which are believed to originate mainly from flat urothelial tumors or, less frequently, from papillary carcinomas, progressively lost CD44 proteins as they penetrated deeper and became less differentiated. This change was paralleled at the mRNA level, by the gradual loss of expression of CD44s and CD44v transcripts in deeply invasive tumors until they were virtually undetectable. Conversely, papillary tumors contained multiple higher molecular weight transcripts, suggesting that the loss of CD44 proteins in the more aggressive tumors is due to a disturbance in transcription. This concept was confirmed by in situ hybridization studies with a probe showing that substantial variant CD44 mRNA is located in the urothelium in papillary carcinomas but is absent from deeply invasive carcinomas. These results indicate that initially there is a striking increase in CD44 gene expression in early bladder carcinomas, relative to normal urothelium, but that this diminishes as the tumors acquire a more aggressive phenotype.
AB - This study investigated CD44 gene expression at both the RNA and protein level in well differentiated superficial and in deeply invasive bladder carcinomas. Proteins were studied by immunohistochemistry using antibodies against standard (CD44s) and variant (CD44v) isoforms. mRNA was analyzed by reverse transcriptase polymerase chain reaction/Southern blotting and in situ hybridization. Immunostaining with antibodies against CD44s and CD44v2, -5 and -6 (exons 7, 10, and 11, respectively) showed that carcinoma cells in all papillary tumors expressed strong signals throughout the epithelium but especially in the basal layer, which abuts on the stroma. However, invasive tumors, which are believed to originate mainly from flat urothelial tumors or, less frequently, from papillary carcinomas, progressively lost CD44 proteins as they penetrated deeper and became less differentiated. This change was paralleled at the mRNA level, by the gradual loss of expression of CD44s and CD44v transcripts in deeply invasive tumors until they were virtually undetectable. Conversely, papillary tumors contained multiple higher molecular weight transcripts, suggesting that the loss of CD44 proteins in the more aggressive tumors is due to a disturbance in transcription. This concept was confirmed by in situ hybridization studies with a probe showing that substantial variant CD44 mRNA is located in the urothelium in papillary carcinomas but is absent from deeply invasive carcinomas. These results indicate that initially there is a striking increase in CD44 gene expression in early bladder carcinomas, relative to normal urothelium, but that this diminishes as the tumors acquire a more aggressive phenotype.
UR - http://www.scopus.com/inward/record.url?scp=0029750232&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029750232&partnerID=8YFLogxK
M3 - Article
C2 - 8780391
AN - SCOPUS:0029750232
SN - 0002-9440
VL - 149
SP - 873
EP - 882
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 3
ER -