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Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases

Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases
Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases
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.
Bag-1, oral cancer, apoptosis
1096-9896
60-71
Hague, Angela
0e1199e4-08c3-4e8b-b40f-2fc61555e6f4
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Huntley, Suzanne
48312d47-2fe1-4757-90d6-fcdca74090b2
Shefford, Kathryn
a33a0c1d-2636-4ce6-b463-d64e124477a1
Eveson, John W.
426a0762-e7a2-488c-ae6d-83ea836de489
Hague, Angela
0e1199e4-08c3-4e8b-b40f-2fc61555e6f4
Packham, Graham
fdabe56f-2c58-469c-aadf-38878f233394
Huntley, Suzanne
48312d47-2fe1-4757-90d6-fcdca74090b2
Shefford, Kathryn
a33a0c1d-2636-4ce6-b463-d64e124477a1
Eveson, John W.
426a0762-e7a2-488c-ae6d-83ea836de489

Hague, Angela, Packham, Graham, Huntley, Suzanne, Shefford, Kathryn and Eveson, John W. (2002) Deregulated Bag-1 protein expression in human oral squamous cell carcinomas and lymph node metastases. The Journal of Pathology, 197 (1), 60-71. (doi:10.1002/path.1076).

Record type: Article

Abstract

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.

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Published date: 2002
Keywords: Bag-1, oral cancer, apoptosis

Identifiers

Local EPrints ID: 26338
URI: http://eprints.soton.ac.uk/id/eprint/26338
ISSN: 1096-9896
PURE UUID: 2e22d6d7-03b2-45f9-94a2-6ae54b0b9699
ORCID for Graham Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 20 Apr 2006
Last modified: 19 Nov 2019 01:52

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