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Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder.
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MedLine Citation:
PMID:  1673627     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The structure and expression of the proto-oncogene c-erbB-2 was studied in 86 patients with transitional cell carcinoma. Initial tissue samples comprised 37 grade 1, 32 grade 2 and 13 grade 3 tumours and four cases of carcinoma in situ. At the time of this first tumour sample, amplification of the c-erbB-2 gene was demonstrated by Southern blotting in 1/37 grade 1, 5/32 grade 2 and 6/13 grade 3 tumours (0.005 less than P less than 0.01). Tumour 're-occurrences' were obtained from 23 of these patients on one or more occasions. Amplification was detected in re-occurrences from seven of these 23, none of whom showed amplification in the first tumour sample. DNA was also extracted from exfoliated cells in urine collected from five cases of carcinoma in situ and c-erbB-2 amplification was demonstrated in one of these. No gene amplification was identified in patients' lymphocytes, ten biopsies of normal urothelium and 22 various intravesical pathologies. Increased expression of c-erbB-2 mRNA correlated with amplification of the gene. In addition, raised levels of mRNA were seen in the absence of gene amplification in six tumours. Immunoblotting using the polyclonal antibody 21N, raised against the c-terminus of the c-erbB-2 protein demonstrated increased amounts of a 185 kD immunoreactive protein in tumours with increased c-erbB-2 gene copy number compared with control tissues. In some tumours with high c-erbB-2 gene copy number, a 155 kD immunoreactive protein not detected in controls was expressed at higher level than the 185 kD protein. Immunocytochemistry using a monoclonal antibody AB-3, raised against the c-terminus of the c-erbB-2 protein, showed a positive reaction in the cytoplasm and cell membrane of tumours with gene amplification and in 40% of tumours with no amplification. An association was found between c-erbB-2 amplification and over-expression and the development of tumour re-occurrences. We suggest that c-erbB-2 amplification and over-expression may provide a useful molecular marker in transitional cell carcinoma of the bladder and merits further investigation as a potential prognostic indicator.
Authors:
L M Coombs; D A Pigott; E Sweeney; A J Proctor; M E Eydmann; C Parkinson; M A Knowles
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of cancer     Volume:  63     ISSN:  0007-0920     ISO Abbreviation:  Br. J. Cancer     Publication Date:  1991 Apr 
Date Detail:
Created Date:  1991-06-04     Completed Date:  1991-06-04     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0370635     Medline TA:  Br J Cancer     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  601-8     Citation Subset:  IM    
Affiliation:
Epithelial Carcinogenesis Laboratory, Marie Curie Research Institute, Oxted, Surrey, UK.
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MeSH Terms
Descriptor/Qualifier:
Blotting, Northern
Blotting, Southern
Carcinoma, Transitional Cell / genetics*,  metabolism
DNA Probes
DNA, Neoplasm / genetics
Follow-Up Studies
Gene Amplification / genetics*
Gene Expression / genetics
Humans
Immunoblotting
Immunoenzyme Techniques
Neoplasm Proteins / biosynthesis,  genetics*
Nucleic Acid Hybridization
Proto-Oncogene Proteins / biosynthesis,  genetics*
RNA, Neoplasm / genetics
Receptor, erbB-2
Urinary Bladder Neoplasms / genetics*,  metabolism
Chemical
Reg. No./Substance:
0/DNA Probes; 0/DNA, Neoplasm; 0/Neoplasm Proteins; 0/Proto-Oncogene Proteins; 0/RNA, Neoplasm; EC 2.7.10.1/Receptor, erbB-2
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Full Text
Journal Information
Journal ID (nlm-ta): Br J Cancer
ISSN: 0007-0920
ISSN: 1532-1827
Article Information
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Print publication date: Month: 4 Year: 1991
Volume: 63 Issue: 4
First Page: 601 Last Page: 608
ID: 1972370
PubMed Id: 1673627

Amplification and over-expression of c-erbB-2 in transitional cell carcinoma of the urinary bladder.
L. M. Coombs
D. A. Pigott
E. Sweeney
A. J. Proctor
M. E. Eydmann
C. Parkinson
M. A. Knowles
Epithelial Carcinogenesis Laboratory, Marie Curie Research Institute, Oxted, Surrey, UK.



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  • Research Article


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