Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

The detection of circulating breast cancer cells in blood could be of special interest as an indicator of diagnosis and prognosis, and for the selection of treatment. In a previous report, our research group determined gene expression profiles in samples of breast cancer tissue, identifying over-expression of the BIK/NBK mRNA gene in 90% of the analyzed samples. In this paper, we analyze the BIK/NBK gene expression as a possible biomarker of circulating breast cancer cells in blood. We demonstrate that the BIK/NBK gene expression is not a significant biomarker in the detection of circulating breast cancer cells in the blood of women with breast cancer. Several studies have evaluated the regulation of apoptosis by estrogens in breast cancer cells, demonstrating the importance of BIK/NBK protein, in estrogen-regulated breast cancer cell apoptosis, which suggests that the regulation of its expression may be an important therapeutic target or strategy in the management of cancer, and, although we did not find statistically significant differences among the patient groups to demonstrate that BIK/NBK gene expression is a biomarker of circulating breast cancer cells in blood, we consider it necessary to continue the study of this gene in breast cancer tissue and its role in the development and progression of breast cancer, its prognostic value, and its potential use as therapeutic target.

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Gene Expression Profiles of Different Breast Cancer Cells Compared with their Responsiveness to Fermented Mistletoe (Viscum album L.) Extracts Iscador from Oak (Quercus), Pine (Pinus), White Fir (Abies) and Apple Tree (Malus) in vitro

Arzneimittelforschung ◽

10.1055/s-0031-1296816 ◽

2011 ◽

Vol 56 (06) ◽

pp. 483-496 ◽

Cited By ~ 1

Author(s):

Jenny Eggenschwiler ◽

Andrea Patrignani ◽

Ulrich Wagner ◽

Hubert Rehrauer ◽

Ralph Schlapbach ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Apple Tree ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Viscum Album ◽

White Fir

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Synergistic antitumor efficacy and altered gene expression signature in breast cancer cells treated with immunotoxins and cyclosporin A

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.13505 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 13505-13505

Author(s):

O. Fodstad ◽

Y. Xi ◽

K. Risberg ◽

J. Ju ◽

Y. G. Anderson

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Protein Synthesis ◽

Breast Cancer Cells ◽

Gene Expression Analysis ◽

Synergistic Effects ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Gene Expression Signature

13505 Background: Immunotoxins (ITs) has shown limited clinical success related to liver toxicity and development of anti-IT antibodies. To delay the immune response we tested combinations of ITs and the Cyclosporin A (CsA). we have shown that one IT, currently in a phase I/II clinical trial, acts by inducing apoptosis and protein synthesis inhibition, but gene expression analysis of IT treated cells has never been reported. Hence, we also studied changes in gene expression induced by ITs alone and the effects of adding (CsA) on both treatment efficacy and gene expression signature. Methods: Human MA-11 breast cancer cells were treated in vitro with antiEGFR- and antiEPCAM-based ITs alone and in combinations with CsA. Therapeutic efficay was assessed by MTS cell viability assay. Total RNA from untreated and treated cells was isolated and CodeLink Uniset Human 20 k Oligo Bioarray (GE Healthcare, Amersham Biosciences, NJ), containing approximately 20,289 gene probes, was used to generate gene expression profiles. Gene expression analysis was carried out using GeneSpring software version 7.2 using One-way ANOVA with p<0.05. Comparisons of gene list across different groups were performed using Venn Diagrams. Results: Combination therapy produced remarkable synergistic effects in MA-11 cells in vitro and in metastasis models in vivo. Moreover, in conventional rats receiving repeated injections of ITs and CsA the formation of anti-IT antibodies was virtually abrogated. Changes in gene expression profiles induced by the ITs alone and in combination with CsA were evaluated to elucidate the underlying molecular mechanisms for the synergistic effects. The ITs each induced specific changes in expression of some apoptosis-related genes but also fogenes in pathways unrelated to apoptosis and protein synthesis. The addition of CsA induced up- or down-regulation of a number of interesting non-immune-associated genes Conclusions: Important shortcomings for successful clinical use of ITs may be overcome by combination therapy with CsA. The possibility for further improvement is provided by results of gene profiling studies identifying therapy-induced genes belonging to different cell signaling pathways. No significant financial relationships to disclose.

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