Identification of an ataxia telangiectasia-mutated protein mediated surveillance system to regulate Bcl-2 overexpression

Zhang, J; Lahti, Jill M.; Bruce, Anthony; He, Lizhi; Parihar, Kavita; Fan, Catherine; Grenet, José; Liu, L; Kidd, Vincent J.; Cormier, Sara L.; Tang, Damu

doi:10.1038/sj.onc.1209565

Cited by 3 publications

(3 citation statements)

References 48 publications

(60 reference statements)

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“…Several covariate mechanisms are responsible for multi-drug resistance in breast cancer cells including increased drug efflux (P-glycoprotein-P-gp), CSCs (CD24), drug detoxification (glutathione S-transferase) deregulated apoptosis (Bcl-2 overexpression) and overexpression of cytokines (SCF ) [8]. The anti-apoptotic expression of Bcl-2 is well documented and its affects on tumourigenic activity [14]. CD24 is a phenotypic surface marker for granulocytes, Bcl’s and CSCs, which are implicated in resistance to both chemotherapy and radiotherapy.…”

Section: Discussionmentioning

confidence: 99%

The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells

Jelly

Hussain

Eremin

et al. 2012

Cancer Cell International

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BackgroundThe outcome of chemotherapy in breast cancer is strongly influenced by multidrug resistance (MDR). Several surrogate markers of chemoresistance have been identified including - CD24 (cluster differentiation 24) expression, stem cell growth factor (SCF), B-cell lymphocyte protein 2 (Bcl-2) and annexin V. The present study aimed to examine the expression of CD24 in the sensitive breast cancer cell line MCF-7 (Michigan Foudation-7) and MCF-7/adriamycin resistant (MCF-7/AdrRes) cells, and, if minimal effective doses of the anthracycline drug adriamycin (0.579 μM and 88.2 μM) would be enhanced by the antibody to SCF (anti-SCF).MethodsCD24 expression was analysed by flow cytometry. Both Bcl-2 and annexin V protein expression were quantitatively assessed by the enzyme-linked immunosorbent assay (ELISA).ResultsIn MCF-7/AdrRes cells the expression of CD24 was significantly higher compared to MCF-7 cells, 86.6% and 16.3% (p < 0.001), respectively. Bcl-2 expression was significantly increased in the presence of adriamycin and SCF (p < 0.038) and decreased in the presence of adriamycin and anti-SCF. When adriamycin, anti-SCF and SCF were combined or when adriamycin was used alone the decrease in Bcl-2 expression was insignificantly altered. In the presence of both adriamycin and SCF the expression of annexin V was decreased. However, it was significantly increased in the presence of adriamycin and anti-SCF (p < 0.042), as well as adriamycin, anti-SCF and SCF combined.In MCF-7 cells the effect of adriamycin alone or with either SCF, anti-SCF or anti-SCF or SCF combined, did not significantly alter the expression of Bcl-2. However, in the presence of both adriamycin and SCF the expression of annexin V was decreased, but was significantly increased in the presence of adriamycin and anti-SCF (p < 0.001), adriamycin, anti-SCF and SCF combined and adriamycin alone. Our results demonstrate that anti-SCF with low dose of adriamycin reduces Bcl-2 expression in MCF-7/AdrRes cells and increases annexin V expression in both MCF7/AdrRes and MCF-7 cells.ConclusionAdding anti-SCF to the chemotherapeutic regime of adriamycin may strongly enhance its chemotherapeutic effect in the treatment of patients with breast cancer.

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Section: Discussionmentioning

confidence: 99%

The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells

Jelly

Hussain

Eremin

et al. 2012

Cancer Cell International

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“…Consistent with this conclusion, unchallenged t(14:18) cells, which express high levels of Bcl-2, show spontaneous, high levels of g-H2AX foci (present data and ref. 44). The significance of these points is underscored by the fact that the presence of DSB and activation of DNA damage signaling are detected in precancerous tissues, interpreted as a consequence of endogenous replication stress, and proposed as initial events of tumorigenesis (45,46).…”

Section: Bcl-2 Represses Hr Via Retention Of Brca1 In Organellesmentioning

confidence: 99%

Bcl-2 Inhibits Nuclear Homologous Recombination by Localizing BRCA1 to the Endomembranes

et al. 2011

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Genetic stability requires coordination of a network of pathways including DNA repair/recombination and apoptosis. In addition to its canonical anti-apoptotic role, Bcl-2 negatively impacts genome stability. In this study, we identified the breast cancer tumor suppressor BRCA1, which plays an essential role in homologous recombination (HR), as a target for Bcl-2 in the repression of HR. Indeed, ionizing radiation-induced BRCA1 foci assembly was repressed when Bcl-2 was expressed ectopically, in human SV40 fibroblasts, or spontaneously, in lymphoma t(14:18) cells and in HeLa and H460 cancer cell lines. Moreover, we showed that the transmembrane (TM) domain of Bcl-2 was required for both inhibition of BRCA1 foci assembly and the inhibition of HR induced by a double-strand break targeted into an intrachromosomal HR substrate by the meganuclease I-SceI. Fluorescence confocal microscopy, proximity ligation assay, and electron microscopy analyses as well as Western blot analysis of subcellular fractions showed that Bcl-2 and BRCA1 colocalized to mitochondria and endoplasmic reticulum in a process requiring the TM domain of Bcl-2. Targeting BRCA1 to the endomembranes depletes BRCA1 from the nucleus and, thus, accounts for the inhibition of HR. Furthermore, our findings support an apoptosis-stimulatory role for the cytosolic form of BRCA1, suggesting a new tumor suppressor function of BRCA1. Together, our results reveal a new mode of BRCA1 regulation and for HR in the maintenance of genome stability. Cancer Res; 71(10); 3590-602. Ó2011 AACR.

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“…Since tamoxifen exhibits antiestrogenic activities in breast cancer cells, this study indicated that tamoxifen up-regulated the expression of ERα and exerted its antagonistic effect through ERα in MCF-7 cells [24]. Although bcl-2 is an anti-apoptotic protein that inhibits apoptosis, it has also been reported to be involved in the surveillance of oncogenesis and the suppression of tumorigenesis [25]. Therefore, the up-regulation of bcl-2 gene may explain the effect of tamoxifen in decreasing cell proliferation in MCF-7 cells.…”

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confidence: 94%

The Combinatory Effects of Glabridin and Tamoxifen on Ishikawa and MCF-7 Cell Lines

Soe

Wei

Yin

2015

Natural Product Communications

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Estrogen replacement therapy is commonly used to replace the loss of estrogen in post-menopausal women. However, it is not suitable to be used in women taking tamoxifen as both of the drugs increase the risk of endometrial cancer. This project aimed to study the potential of using the natural compound glabridin in combination with tamoxifen as a drug for estrogen replacement therapy. Ishikawa and MCF-7 cells were used to investigate the estrogenic activities stimulated by the combination of tamoxifen and glabridin through ALP and MTT assays. The expressions of the ESR1 and bcl-2 genes have also been determined using RT-PCR. The results indicated that the combination of 1×10-5 M tamoxifen and 1×10-6 M glabridin exhibited estrogenic activities and suppressed cell growth in both cell lines. The relative expressions of ESR1 and bcl-2 genes indicated that the estrogenicity expressed by the combinatory drug was regulated by estrogen receptor α; however, the reduction in cell proliferation was not modulated by bcl-2 anti-apoptotic proteins. These results suggested that the combination of tamoxifen and glabridin has potential to be used as an estrogen replacement drug with a reduced risk of endometrial cancer that has arisen from the intake of tamoxifen.

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Identification of an ataxia telangiectasia-mutated protein mediated surveillance system to regulate Bcl-2 overexpression

Cited by 3 publications

References 48 publications

The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells

The stem cell factor antibody enhances the chemotherapeutic effect of adriamycin on chemoresistant breast cancer cells

Bcl-2 Inhibits Nuclear Homologous Recombination by Localizing BRCA1 to the Endomembranes

The Combinatory Effects of Glabridin and Tamoxifen on Ishikawa and MCF-7 Cell Lines

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