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BAG-1 expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data

BAG-1 expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data
BAG-1 expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data
BAG-1 (BCL-2 athanogene-1), a multifunctional protein which associates with steroid hormone receptors (including the oestrogen receptor) and the anti-apoptotic BCL-2 protein, regulates steroid hormone-dependent transcription and apoptosis. Direct interaction with 70 kD heat-shock proteins, HSC70 and HSP70, may mediate the diverse functions of BAG-1. Immunohistochemistry was used to examine the expression of BAG-1 and HSC70 in 160 cases of invasive breast cancer. BAG-1 was expressed in 92% of cases; most tumours exhibited cytoplasmic BAG-1, while a smaller proportion also had nuclear immunostaining. There was a significant inverse correlation between histological grade and nuclear BAG-1 expression, with higher-grade tumours tending to have reduced nuclear BAG-1 expression, but there was no association with cytoplasmic BAG-1. There was also no significant correlation between nuclear or cytoplasmic BAG-1 expression and oestrogen receptor positivity. Since BAG-1 may be influenced by hormonal background, the relationship between grade and oestrogen receptor was examined separately in pre-menopausal and post-menopausal women. The statistically significant correlation between nuclear BAG-1 expression and low tumour grade was strong in pre-menopausal, but not apparent in post-menopausal women. A statistically significant correlation was observed between cytoplasmic, but not nuclear, BAG-1 expression and oestrogen receptor status in pre-menopausal, but not post-menopausal, women. There was no correlation between BAG-1 protein expression and RNA, suggesting that important post-transcriptional mechanisms control BAG-1 expression in vivo. HSC70 was also detected in the majority (97%) of cases, although expression was not correlated with BAG-1 levels, oestrogen receptor status or tumour grade. Overall survival in cases with high levels of nuclear BAG-1 expression was improved, though not significantly. These results are consistent with the hypothesis that BAG-1 plays an important but variable role in breast cancers developing in pre-menopausal and post-menopausal women.
BAG-1, breast cancer, HSP70, HSC70
51-59
Townsend, P.A.
89300833-c898-4ae1-a3b2-03214c71da52
Dublin, E.
626493e4-daa8-485f-9209-7ec4acef6690
Hart, I.R.
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Kao, R.H.
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Hanby, A.M.
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Cutress, R.I.
68ae4f86-e8cf-411f-a335-cdba51797406
Poulsom, R.
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Ryder, K.
88a9c398-291d-4f33-a874-b25d9114cdba
Barnes, D.M.
d9552c52-d61a-4f7c-a89a-1ff82cfb299a
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394
Townsend, P.A.
89300833-c898-4ae1-a3b2-03214c71da52
Dublin, E.
626493e4-daa8-485f-9209-7ec4acef6690
Hart, I.R.
7bfb93f0-86c5-4200-af57-fd7f251076c1
Kao, R.H.
ec96d285-e5ba-4ab2-aec1-786cfde8c2da
Hanby, A.M.
b9ad1aae-ee74-453d-8975-e2461b2bb831
Cutress, R.I.
68ae4f86-e8cf-411f-a335-cdba51797406
Poulsom, R.
2d9bb2a4-78a7-4f86-97ea-38c40d0e0db9
Ryder, K.
88a9c398-291d-4f33-a874-b25d9114cdba
Barnes, D.M.
d9552c52-d61a-4f7c-a89a-1ff82cfb299a
Packham, G.
fdabe56f-2c58-469c-aadf-38878f233394

Townsend, P.A., Dublin, E., Hart, I.R., Kao, R.H., Hanby, A.M., Cutress, R.I., Poulsom, R., Ryder, K., Barnes, D.M. and Packham, G. (2002) BAG-1 expression in human breast cancer: interrelationship between BAG-1 RNA, protein, HSC70 expression and clinico-pathological data. The Journal of Pathology, 197 (1), 51-59. (doi:10.1002/path.1081). (PMID:12081204)

Record type: Article

Abstract

BAG-1 (BCL-2 athanogene-1), a multifunctional protein which associates with steroid hormone receptors (including the oestrogen receptor) and the anti-apoptotic BCL-2 protein, regulates steroid hormone-dependent transcription and apoptosis. Direct interaction with 70 kD heat-shock proteins, HSC70 and HSP70, may mediate the diverse functions of BAG-1. Immunohistochemistry was used to examine the expression of BAG-1 and HSC70 in 160 cases of invasive breast cancer. BAG-1 was expressed in 92% of cases; most tumours exhibited cytoplasmic BAG-1, while a smaller proportion also had nuclear immunostaining. There was a significant inverse correlation between histological grade and nuclear BAG-1 expression, with higher-grade tumours tending to have reduced nuclear BAG-1 expression, but there was no association with cytoplasmic BAG-1. There was also no significant correlation between nuclear or cytoplasmic BAG-1 expression and oestrogen receptor positivity. Since BAG-1 may be influenced by hormonal background, the relationship between grade and oestrogen receptor was examined separately in pre-menopausal and post-menopausal women. The statistically significant correlation between nuclear BAG-1 expression and low tumour grade was strong in pre-menopausal, but not apparent in post-menopausal women. A statistically significant correlation was observed between cytoplasmic, but not nuclear, BAG-1 expression and oestrogen receptor status in pre-menopausal, but not post-menopausal, women. There was no correlation between BAG-1 protein expression and RNA, suggesting that important post-transcriptional mechanisms control BAG-1 expression in vivo. HSC70 was also detected in the majority (97%) of cases, although expression was not correlated with BAG-1 levels, oestrogen receptor status or tumour grade. Overall survival in cases with high levels of nuclear BAG-1 expression was improved, though not significantly. These results are consistent with the hypothesis that BAG-1 plays an important but variable role in breast cancers developing in pre-menopausal and post-menopausal women.

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Published date: 2002
Keywords: BAG-1, breast cancer, HSP70, HSC70

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Local EPrints ID: 24993
URI: http://eprints.soton.ac.uk/id/eprint/24993
PURE UUID: 7878c7da-9d3a-401f-a8a3-6021cadf368b
ORCID for G. Packham: ORCID iD orcid.org/0000-0002-9232-5691

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Date deposited: 05 Apr 2006
Last modified: 17 Sep 2019 01:02

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Contributors

Author: P.A. Townsend
Author: E. Dublin
Author: I.R. Hart
Author: R.H. Kao
Author: A.M. Hanby
Author: R.I. Cutress
Author: R. Poulsom
Author: K. Ryder
Author: D.M. Barnes
Author: G. Packham ORCID iD

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