Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer

Nadler, Yasmine; Camp, Robert L.; Giltnane, Jennifer M.; Moeder, Christopher B.; Rimm, David L.; Kluger, Harriet M.; Kluger, Yuval

doi:10.1186/bcr1998

Cited by 52 publications

(57 citation statements)

References 68 publications

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“…So far, the strongest predictive and prognostic factor has been the number of affected lymph nodes (Munster and Norton, 2001), yet within the lymph node-positive subset and the lymph node-negative subset of patients there is variability in prognosis (Nadler et al, 2008). In this study, Bcl-2 was more frequently associated with negative nodal status (100%) in both TNBC and non-TNBC and there was a significant inverse correlation with nodal positivity in non-TNBC group.…”

Section: Discussionmentioning

confidence: 51%

“…On the other hand, Nadler et al (2008), found no association between expression of Bcl-2 and patient's age.…”

Section: Discussionmentioning

confidence: 88%

“…Other studies have also noted that poorly differentiated breast carcinomas lack Bcl-2 reactivity (Bhargava et al, 1994;Park et al, 2002), and others found a significant inverse association with expression of Bcl-2 and increasing tumor grade (Callagy et al, 2006), suggesting that loss of Bcl-2 expression may reflect a loss of differentiation (Bhargava et al, 1994). On the contrary, other studies disclosed no association between expression of Bcl-2 and nuclear grade (Cecka et al, 2008;Nadler et al, 2008).…”

Section: Discussionmentioning

confidence: 91%

“…To identify additional prognostic markers and improve risk stratification for breast cancer, further studies suggested combining protein markers used to define these molecular subtypes (Callagy et al, 2006;Nadler et al, 2008;Dawson et al, 2010). Indeed, they showed that only Bcl-2 added prognostic information independent of the other accepted prognostic factors (Callagy et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

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Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

El-Mageed

Mohamed²,

Elesawy³

2013

Asian Pacific Journal of Cancer Prevention

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Background: Prognostication of breast cancer using clinico-pathologic variables, although useful, remains imperfect. Recent research has focused on finding new markers of prognosis using gene expression profiling. Panels of proteins assessed by immunohistochemistry might also be useful in this regard. This study focused on Bcl-2 protein expression in triple-negative (TNBC) and non-triple-negative breast cancer (non-TNBC) with correlation to clinico-pathologic variables. Materials and methods: We analyzed Bcl-2 expression in 77 women with primary breast carcinoma divided into two groups; triple-negative and non-triple-negative according to expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptors (Her2/neu). Bcl-2 expression was assessed in relation to age, histo-pathological subtype, grade, nodal status and tumor size. Results: Bcl-2 was expressed in 74% of triple-negative breast cancers and 70% of non-triple-negative cancers. In TNBC, expression was significantly correlated with invasive ductal subtype, while in non-TNBC it was significantly correlated with age and negative nodal status. In both groups higher Bcl-2 expression associated with favourable prognostic factors in breast cancer, but no significant statistical correlations were found. Conclusions: Frequency of Bcl-2 expression does not differ between TNBC and non-TNBC, but different prognostic factors correlate with Bcl-2 in the two cases.

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Section: Discussionmentioning

confidence: 51%

“…On the other hand, Nadler et al (2008), found no association between expression of Bcl-2 and patient's age.…”

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

El-Mageed

Mohamed²,

Elesawy³

2013

Asian Pacific Journal of Cancer Prevention

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“…Although these experiments were primarily focused on the role of BAG-1 in the development of the malignant process in the breast, it is nonetheless of interest to speculate how they may relate to the association between high BAG-1 expression and improved outcome for breast cancer patients observed by us and others (Turner et al, 2001;Cutress et al, 2003;Millar et al, 2008;Nadler et al, 2008). One possible explanation for this apparent dichotomy lies in the inherent heterogeneity in BAG-1's actions, such that its pro-survival effects may have an important role during tumor initiation, but lead to the formation of a less aggressive or more therapeutically responsive cancer, for example, through its known effects on nuclear hormone receptor function.…”

Section: Discussionmentioning

confidence: 99%

BAG-1 overexpression attenuates luminal apoptosis in MCF-10A mammary epithelial cells through enhanced RAF-1 activation

2009

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Although the multi-functional, prosurvival protein, Bcl-2-associated anthanogene 1 (BAG-1) is frequently overexpressed in breast cancers, its role in the development or maintenance of the malignant state remains unclear. Here, we have used the established MCF-10A 3-dimensional (3D) model of mammary morphogenesis as a biologically relevant system to determine how BAG-1 expression may influence the development of breast cancer. When cultured in 3D, MCF-10A cells undergo a highly regulated morphogenic program leading to the development of polarized acinar structures containing a central, hollow lumen formed, in part, through the induction of BIM-dependent apoptosis. BAG-1 overexpression resulted in an attenuation of this normal apoptotic program characterized by a significantly increased number of acini with filled lumens-a phenotype commonly observed in ductal carcinoma in situ. BAG-1's effects were associated with an activation of RAF-1-a known binding partner of BAG-1, enhanced signaling through the MAP kinase pathway and a decrease in BIM expression. Reversal of the BAG-1-associated survival phenotype by the mitogen-activated kinase/ERK kinase inhibitor, U0126, implicates the RAF-1-extracellular signal-regulated kinase signaling pathway as a major mediator of BAG-1's effects in this model. As BAG-1 expression is often elevated in preinvasive breast cancers, these findings support a possible role for BAG-1 as an early contributor to the malignant process in the breast.

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A large set of estrogen receptor β‐interacting proteins identified by tandem affinity purification in hormone‐responsive human breast cancer cell nuclei

et al. 2010

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Estrogen receptors α (ER-α) and β (ER-β) play distinct biological roles in onset and progression of hormone-responsive breast cancer, with ER-β exerting a modulatory activity on ER-α-mediated estrogen signaling and stimulation of cell proliferation by mechanisms still not fully understood. We stably expressed human ER-β fused to a tandem affinity purification-tag in estrogen-responsive MCF-7 cells and applied tandem affinity purification and nanoLC-MS/MS to identify the ER-β interactome of this cell type. Functional annotation by bioinformatics analyses of the 303 proteins that co-purify with ER-β from nuclear extracts identify several new molecular partners of this receptor subtype that represents nodal points of a large protein network controlling multiple processes and functions in breast cancer cells.

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Expression patterns and prognostic value of Bag-1 and Bcl-2 in breast cancer

Cited by 52 publications

References 68 publications

Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

Different Prognostic Factors Correlate with Bcl-2 Expression among Triple Negative and Non-Triple Negative Breast Cancers

BAG-1 overexpression attenuates luminal apoptosis in MCF-10A mammary epithelial cells through enhanced RAF-1 activation

A large set of estrogen receptor β‐interacting proteins identified by tandem affinity purification in hormone‐responsive human breast cancer cell nuclei

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