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

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

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49 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)51-59
Number of pages9
JournalJournal of Pathology
Volume197
Issue number1
DOIs
Publication statusPublished - May 8 2002
Externally publishedYes

Keywords

  • BAG-1
  • Breast cancer
  • HSC70
  • HSP70

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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