BAG-1: A Novel Biomarker Predicting Long-Term Survival in Early-Stage Breast Cancer

Turner, Bruce; Krajewski, Stanisław; Krajewska, Maryla; Takayama, Shinichi; Gumbs, Andrew A.; Carter, Darryl; Rebbeck, Timothy R.; Haffty, Bruce G.; Reed, John C.

doi:10.1200/jco.2001.19.4.992

Cited by 89 publications

(95 citation statements)

References 41 publications

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“…Consistent with studies in other tumour types they found that approximately two thirds of tumours expressed high levels of BAG-1. In particular they found no correlations between BAG-1 and clinico-pathological parameters, but did find that, similar to the study of Turner et al (2001) in breast cancer, cytoplasmic expression of BAG-1 independently correlated with improved overall survival.…”

Section: Bag-1 and Other Malignanciesmentioning

confidence: 64%

“…By contrast, Turner et al (2001) reported no correlation between tumour grade and BAG-1 expression. Correlations with other clinical markers, such as oestrogen receptor alpha (ERa) and BCL-2 expression have been reported in various studies, but these appear to be not as strong as the correlation with grade and are more variably detected (Table 1).…”

Section: Bag-1 and Breast Cancermentioning

confidence: 88%

“…Larger prospective studies should be more representative of the spectrum of breast cancer as a whole and have increased power to detect independent prognostic predictors in multivariate analysis, in particular in the presence of possible confounding associations such as tumour grade and ERa status. As discussed by Turner et al (2001) it is not immediately apparent why an anti-apoptotic protein is associated with good prognosis. This kind of observation is not unique, however, since expression of Bcl-2 is also associated with good prognosis in breast cancer, for example.…”

Section: Discussionmentioning

confidence: 99%

“…Four large immunohistochemical studies of the expression and clinical significance of BAG-1 in breast cancer have been reported and these are summarised in Table 1 (Tang et al, 1999;Turner et al, 2001;Sjostrom et al, 2002;Townsend et al, 2002). Some of the results from these studies are inconsistent and further studies are required to fully understand the role of BAG-1 expression in breast cancer (Cutress et al, 2001).…”

Section: Bag-1 and Breast Cancermentioning

confidence: 99%

“…Correlations with other clinical markers, such as oestrogen receptor alpha (ERa) and BCL-2 expression have been reported in various studies, but these appear to be not as strong as the correlation with grade and are more variably detected (Table 1). Turner et al (2001) reported an overall 10-year survival for women with early stage breast cancer of 82% with high cytoplasmic BAG-1 levels vs 42% survival with low BAG-1 levels. Cytoplasmic BAG-1 status predicted outcome in both univariate and multivariate analyses, and also retained predictive value in a subset of their patients with pathologically negative lymph nodes.…”

Section: Bag-1 and Breast Cancermentioning

confidence: 99%

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BAG-1 expression and function in human cancer

et al. 2002

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BAG-1 is a multifunctional protein that interacts with a wide range of target molecules to regulate apoptosis, proliferation, transcription, metastasis and motility. Interaction with chaperone molecules may mediate many of the effects of BAG-1. The pathways regulated by BAG-1 play key roles in the development and progression of cancer and determining response to therapy, and there has been considerable interest in determining the clinical significance of BAG-1 expression in malignant cells. There is an emerging picture that BAG-1 expression is frequently altered in a range of human cancers relative to normal cells and a recent report suggests the exciting possibility that BAG-1 expression may have clinical utility as a prognostic marker in early breast cancer. However, other studies of BAG-1 expression in breast cancer and other cancer types have yielded differing results. It is important to view these findings in the context of current knowledge of BAG-1 expression and function. This review summarises recent progress in understanding the clinical significance of BAG-1 expression in cancer in light of our understanding of BAG-1 function.

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Section: Bag-1 and Other Malignanciesmentioning

confidence: 64%

Section: Bag-1 and Breast Cancermentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Bag-1 and Breast Cancermentioning

confidence: 99%

Section: Bag-1 and Breast Cancermentioning

confidence: 99%

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BAG-1 expression and function in human cancer

et al. 2002

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Prognostic significance of BAG-1 expression in nonsmall cell lung cancer

et al. 2001

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Overexpressed nuclear BAG‐1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin

Chen

Zhou

et al. 2013

J of Cellular Biochemistry

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Bcl-2-associated athanogene-1 (BAG-1) is a multifunctional anti-apoptotic protein which regulates an array of cellular processes, including apoptosis, signaling, proliferation, transcription, and cell motility and has been reported to be over-expressed in a number of human malignancies. To investigate the possible involvement of BAG-1 in tumorigenesis of hepatocellular carcinoma (HCC), we performed Western blot analysis in eight paired samples of HCC and adjacent peritumoral tissues and immunohistochemistry in 65 paraffin sections of HCC, which both showed an enhanced expression of nuclear BAG-1 isoform in HCC tissues. Statistical analysis confirmed that overexpression of nuclear BAG-1 in HCC tissues was significantly associated with histological grading (P < 0.001), poor prognosis (P = 0.004), and was found to be an independent prognostic indicator for HCC (P = 0.023). We also noted that BAG-1 was overexpressed in four HCC cell lines compared with a normal hepatocyte cell line, and BAG-1 overexpression increased resistance of HCC cells to doxorubicin, a common chemotherapeutic agent for HCC. Furthermore, we observed that knock down of BAG-1 with siRNA in HepG2 cells increased the chemosensitivity of cells, a process mediated through inhibition of doxorubicin-triggered NF-κB activation; and knock down of BAG-1 suppressed proliferation and cell cycle transition of HepG2 cells. In consequence, our results for the first time indicated that BAG-1 was dysregulated in HCC and suppression of BAG-1 expression which resulted in inhibiting of NF-κB signaling might be developed into a new strategy in HCC therapy.

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BAG-1: A Novel Biomarker Predicting Long-Term Survival in Early-Stage Breast Cancer

Abstract: These findings provide preliminary evidence that BAG-1 represents a potential marker of improved survival in early-stage breast cancer patients, independent of the status of axillary lymph nodes.

Cited by 89 publications

References 41 publications

BAG-1 expression and function in human cancer

BAG-1 expression and function in human cancer

Prognostic significance of BAG-1 expression in nonsmall cell lung cancer

Overexpressed nuclear BAG‐1 in human hepatocellular carcinoma is associated with poor prognosis and resistance to doxorubicin

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