Document Detail


Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases.
MedLine Citation:
PMID:  12081206     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bag-1 is an anti-apoptotic protein that promotes metastasis in some tumour cell types. To determine whether Bag-1 expression is altered in 64 oral squamous cell carcinomas, tumour samples were compared with 17 samples of normal oral epithelium. Normal oral epithelia had pronounced nuclear staining in the basal and maturation layers and weak cytoplasmic staining that was most pronounced in the basal and suprabasal layers. Oral squamous cell carcinomas demonstrated a tendency for reduced nuclear staining intensity (p=0.036). Cytoplasmic staining intensity was not significantly different between tumour and normal tissue. However, many tumours were observed to have less of a difference between nuclear staining intensity and cytoplasmic staining intensity than normal oral epithelium. Furthermore, in lymph node metastases, cytoplasmic Bag-1 staining was stronger in 8/13 cases than in corresponding primary tumours (p=0.021). Western blotting using nine oral primary carcinoma cell lines and four normal keratinocyte cultures showed that the isoforms Bag-1s, Bag-1M, and Bag-1L were expressed in normal and malignant oral epithelial cells. Bag-1L unique sequences were shown to adopt an exclusively nuclear, and predominantly nucleolar, localization by use of transiently transfected N-terminal Bag-1L-EGFP. However, levels of Bag-1L in carcinoma cells did not differ significantly from those of normal keratinocytes. Therefore the reduced nuclear staining observed in oral squamous cell carcinomas compared with normal epithelium may reflect changes in the localization of Bag-1 isoforms, rather than decreased expression of Bag-1L. Alterations in the relative proportions of Bag-1S, Bag-1M, and Bag-1L were detected in 6/9 oral carcinoma cell lines; 5/9 oral carcinoma cell lines had a significantly greater proportion of Bag-1M than normal keratinocytes and in another cell line, Bag-1L was significantly underrepresented. Overall, the results suggest that Bag-1 deregulation plays a role in oral carcinogenesis at two different stages: during primary carcinoma development and during lymph node metastasis.
Authors:
Angela Hague; Graham Packham; Suzanne Huntley; Kathryn Shefford; John W Eveson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of pathology     Volume:  197     ISSN:  0022-3417     ISO Abbreviation:  J. Pathol.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-06-25     Completed Date:  2002-07-12     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0204634     Medline TA:  J Pathol     Country:  England    
Other Details:
Languages:  eng     Pagination:  60-71     Citation Subset:  IM    
Affiliation:
Department of Oral and Dental Science, University of Bristol, Bristol Dental Hospital and School, UK. a.hague@bristol.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Adult
Apoptosis
Carcinoma, Squamous Cell / metabolism*,  pathology
Carrier Proteins / metabolism*
Cell Nucleus / metabolism
Cytoplasm / metabolism
DNA-Binding Proteins
Female
Humans
Keratinocytes / metabolism
Lymphatic Metastasis
Male
Middle Aged
Mouth Mucosa / metabolism
Mouth Neoplasms / metabolism*,  pathology
Neoplasm Proteins / metabolism*
Neoplasm Staging
Protein Isoforms / metabolism
Transcription Factors
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/BCL2-associated athanogene 1 protein; 0/Carrier Proteins; 0/DNA-Binding Proteins; 0/Neoplasm Proteins; 0/Protein Isoforms; 0/Transcription Factors

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