Progressive loss of CD44 gene expression in invasive bladder cancer

Takashi Sugino, Hazel Gorham, Kazuhiro Yoshida, John Bolodeoku, Vinod Nargund, David Cranston, Steven Goodison, David Tarin

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)873-882
Number of pages10
JournalAmerican Journal of Pathology
Volume149
Issue number3
StatePublished - Sep 1 1996
Externally publishedYes

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Urinary Bladder Neoplasms
Gene Expression
Neoplasms
Carcinoma
Urothelium
Papillary Carcinoma
Messenger RNA
In Situ Hybridization
Urinary Bladder
Proteins
Antibodies
Southern Blotting
Reverse Transcriptase Polymerase Chain Reaction
Exons
Protein Isoforms
Epithelium
Molecular Weight
Immunohistochemistry
RNA
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Sugino, T., Gorham, H., Yoshida, K., Bolodeoku, J., Nargund, V., Cranston, D., ... Tarin, D. (1996). Progressive loss of CD44 gene expression in invasive bladder cancer. American Journal of Pathology, 149(3), 873-882.

Progressive loss of CD44 gene expression in invasive bladder cancer. / Sugino, Takashi; Gorham, Hazel; Yoshida, Kazuhiro; Bolodeoku, John; Nargund, Vinod; Cranston, David; Goodison, Steven; Tarin, David.

In: American Journal of Pathology, Vol. 149, No. 3, 01.09.1996, p. 873-882.

Research output: Contribution to journalArticle

Sugino, T, Gorham, H, Yoshida, K, Bolodeoku, J, Nargund, V, Cranston, D, Goodison, S & Tarin, D 1996, 'Progressive loss of CD44 gene expression in invasive bladder cancer', American Journal of Pathology, vol. 149, no. 3, pp. 873-882.
Sugino T, Gorham H, Yoshida K, Bolodeoku J, Nargund V, Cranston D et al. Progressive loss of CD44 gene expression in invasive bladder cancer. American Journal of Pathology. 1996 Sep 1;149(3):873-882.
Sugino, Takashi ; Gorham, Hazel ; Yoshida, Kazuhiro ; Bolodeoku, John ; Nargund, Vinod ; Cranston, David ; Goodison, Steven ; Tarin, David. / Progressive loss of CD44 gene expression in invasive bladder cancer. In: American Journal of Pathology. 1996 ; Vol. 149, No. 3. pp. 873-882.
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