title: High level expression of differentially localized BAG-1 isoforms in some oestrogen receptor-positive human breast cancers.
abstract: Sensitivity to oestrogens and apoptosis are critical determinants of the development and progression of breast cancer and reflect closely linked pathways in breast epithelial cells. For example, induction of BCL-2 oncoprotein expression by oestrogen contributes to suppression of apoptosis and BCL-2 and oestrogen receptor (ER) are frequently co-expressed in tumours. BAG-1/HAP is a multifunctional protein which complexes with BCL-2 and steroid hormone receptors (including the ER), and can suppress apoptosis and influence steroid hormone-dependent transcription. Therefore, analysis of expression of BAG-1 in human breast cancer is of considerable interest. BAG-1 was readily detected by immunostaining in normal breast epithelial cells and most ER-positive tumours, but was undetectable or weakly expressed in ER-negative tumours. BAG-1 positive cells showed a predominantly cytoplasmic or cytoplasmic plus nuclear distribution of staining. A correlation between ER and BAG-1 was also evident in breast cancer derived cell lines, as all lines examined with functional ER expression also expressed high levels of BAG-1. In addition to the prototypical 36 kDa BAG-1 isoform, breast cancer cells expressed higher molecular weight isoforms and, in contrast to BCL-2, BAG-1 expression was independent of oestrogens. BAG-1 isoforms were differentially localized to the nucleus or cytoplasm and this was also independent of oestrogens. These results demonstrate a close association between BAG-1 and functional ER expression and suggest BAG-1 may be useful as a therapeutic target or prognostic marker in breast cancer.
authors.affiliation: Ludwig Institute for Cancer Research, Imperial College of Medicine, St Mary's Campus, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Brimmell
authors.forename: J S
authors.initials: JS
authors.lastname: Burns
authors.forename: P
authors.initials: P
authors.lastname: Munson
authors.forename: L
authors.initials: L
authors.lastname: McDonald
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Hare
authors.forename: S R
authors.initials: SR
authors.lastname: Lakhani
authors.forename: G
authors.initials: G
authors.lastname: Packham
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019254:Genes, bcl-2 / Q000235:genetics* / Q000502:physiology; D006801:Humans; D008969:Molecular Sequence Data; D011379:Prognosis; D020033:Protein Isoforms / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
chemical_list: D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D020033:Protein Isoforms; D011960:Receptors, Estrogen