Modulation of tamoxifen sensitivity by antisense <i>Bcl‐2</i> and trastuzumab in breast carcinoma cells

Kim, Ryungsa; Tanabe, Kazuaki; Emi, Manabu; Uchida, Yuzo; Toge, Tetsuya

doi:10.1002/cncr.21029

Cited by 28 publications

(20 citation statements)

References 45 publications

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“…the higher the transfection efficiency, the lower the cell viability. The results confirmed the report of decreasing cell viability in MCF-7 cells treated with bcl-2 antisense [29][30][31]. Our results provided the basis for launching the study to examine the efficacy of bcl-2 antisense and CDDP combination therapy in isogenic MCF-7 cell lines with or without functional p53.…”

Section: Discussionsupporting

confidence: 87%

BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53

et al. 2005

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Chemotherapy has been used for treatment of breast cancer but with limited success. We characterized the effects of bcl-2 antisense and cisplatin combination therapy in two human isogenic breast carcinoma cells p53(+)MCF-7 and p53(-)MCF-7/E6. The transferrin-facilitated lipofection strategy we have developed yielded same transfection efficiency in both cells. Bcl-2 antisense delivered with this strategy significantly induced more cell death, apoptosis, and cytochrome c release in MCF-7/E6 than in MCF-7, but did not affect Fas level in both cells and activated caspase-8 equally. Cisplatin exerted same effects on cell viability and apoptosis in both cells, but released smaller amounts of cytochrome c while activated more caspase-8 in MCF-7/E6. The combination treatment yielded greater effects on cell viability, apoptosis, cytochrome c release, and caspase-8 activation than individual treatments in both cells although p53(-) cells were more sensitive. The potentiated activation of caspase-8 in the combination treatment suggested that caspase-8-mediated (but cytochrome c-independent) apoptotic pathway is the major contributor of the enhanced cell killing. Thus, bcl-2 antisense delivered with transferrin-facilitated lipofection can achieve the efficacy of killing breast cancer cells and sensitizing them to chemotherapy. Bcl-2 antisense and cisplatin combination treatment is a potentially useful therapeutic strategy for breast cancer irrespective of p53 status.

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Section: Discussionsupporting

confidence: 87%

BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53

et al. 2005

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“…The estrogen-dependent expression of BCL-2 has been reported to contribute to the prosurvival effect of estrogen (Teixeira et al, 1995;Perillo et al, 2000). Downregulation of BCL-2 is involved in antiestrogeninduced apoptosis and depletion of BCL-2 expression enhances sensitivity of breast cancer cells to tamoxifen (Diel et al, 1999;Zhang et al, 1999;Kim et al, 2005). BCL-2 is positively associated with ERa expression (Elledge et al, 1997) whereas decreased BCL-2 expression has been observed after induction of ERb expression in T47D mammary carcinoma cells (Williams et al, 2008), concordant with our observation that ERb is decreased and BCL-2 expression is increased by forced expression of ARTN.…”

Section: Discussionmentioning

confidence: 99%

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

et al. 2010

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We have previously identified an oncogenic role of artemin (ARTN), a member of glial cell derived neurotrophic factor family of ligands, in mammary carcinoma. We herein report that ARTN is an estrogen-inducible gene. Metaanalysis of gene expression data sets showed that ARTN expression is positively correlated to estrogen receptor (ER) status in human mammary carcinoma. Furthermore, in patients with ER-positive mammary carcinoma treated with tamoxifen, high ARTN expression is significantly correlated with decreased survival. Forced expression of ARTN in ER-positive human mammary carcinoma cells increased ER transcriptional activity, promoted estrogenindependent growth and produced resistance to tamoxifen and fulvestrant in vitro and to tamoxifen in xenograft models. ARTN-stimulated resistance to tamoxifen and fulvestrant is mediated by increased BCL-2 expression. Conversely, depletion of endogenous ARTN by smallinterfering RNA or functional antagonism of ARTN by antibody enhanced the efficacy of antiestrogens. Tamoxifen decreased ARTN expression in tamoxifen-sensitive mammary carcinoma cells whereas ARTN expression was increased in tamoxifen-resistant cells and not affected by tamoxifen treatment. Antibody inhibition of ARTN in tamoxifen-resistant cells improved tamoxifen sensitivity. Functional antagonism of ARTN therefore warrants consideration as an adjuvant therapy to enhance antiestrogen efficacy in ER-positive mammary carcinoma.

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“…In tamoxifen-resistant breast cancer cells, anti-sense BCL-2 treatment enhanced sensitivity to tamoxifen in HER2-positive cells [43]. In addition, BCL-2 overexpression, causes paclitaxel resistance in MCF-7 cells [44].…”

Section: Discussionmentioning

confidence: 99%

miRNA-34a is associated with docetaxel resistance in human breast cancer cells

Kastl

Brown

Schofield

2011

Breast Cancer Res Treat

169

112

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Docetaxel is a chemotherapy drug to treat breast cancer, however as with many chemotherapeutic drugs resistance to docetaxel occurs in 50% of patients, and the underlying molecular mechanisms of drug resistance are not fully understood. Gene regulation through microRNAs (miRNA) has been shown to play an important role in cancer drug resistance. By directly targeting mRNA, miRNAs are able to inhibit genes that are necessary for signalling pathways or drug induced apoptosis rendering cells drug resistant. This study investigated the role of differential miRNA expression in two in vitro breast cancer cell line models (MCF-7, MDA-MB-231) of acquired docetaxel resistance. MiRNA microarray analysis identified 299 and 226 miRNAs altered in MCF-7 and MDA-MB-231 docetaxel-resistant cells, respectively. Docetaxel resistance was associated with increased expression of miR-34a and miR-141 and decreased expression of miR-7, miR-16, miR-30a, miR-125a-5p, miR-126. Computational target prediction revealed eight candidate genes targeted by these miRNAs. Quantitative PCR and western analysis confirmed decreased expression of two genes, BCL-2 and CCND1, in docetaxel-resistant cells, which are both targeted by miR-34a. Modulation of miR-34a expression was correlated with BCL-2 and cyclin D1 protein expression changes and a direct interaction of miR-34a with BCL-2 was shown by luciferase assay. Inhibition of miR-34a enhanced response to docetaxel in MCF-7 docetaxel-resistant cells, whereas overexpression of miR-34a conferred resistance in MCF-7 docetaxel-sensitive cells. This study is the first to show differences in miRNA expression, in particular, increased expression of miR-34a in an acquired model of docetaxel resistance in breast cancer. This serves as a mechanism of acquired docetaxel resistance in these cells, possibly through direct interactions with BCL-2 and CCND1, therefore presenting a potential therapeutic target for the treatment of docetaxel-resistant breast cancer.

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Modulation of tamoxifen sensitivity by antisense Bcl‐2 and trastuzumab in breast carcinoma cells

Cited by 28 publications

References 45 publications

BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53

BCL-2 antisense and cisplatin combination treatment of MCF-7 breast cancer cells with or without functional p53

Artemin is estrogen regulated and mediates antiestrogen resistance in mammary carcinoma

miRNA-34a is associated with docetaxel resistance in human breast cancer cells

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