Abstract 1402: A reporter mouse model reveals that human CYP19A1 (aromatase) gene expression is induced in breast cancer xenograft stroma and surrounding mammary gland by the cancer cells in vivo.

1074 Background: Imatinib mesylate (imatinib) is a potent and selective inhibitor of the tyrosine kinases, Bcr-Abl, c-Kit and platelet-derived growth factor receptors (PDGFRs). Since its advent for the successful treatment of chronic myelogenous leukemia in 2001, the clinical efficacy of imatinib has been investigated in many other human malignancies, including breast cancer. Based on recent reports that chemotherapy selects more invasive and metastasizing cells, we have hypothesized that exposure of breast cancer cells to imatinib could enhance their malignant behavior. Methods: MA-11 breast carcinoma cells, originating from bone marrow micrometastases, were exposed to imatinib in vitro for seven days. After four days of recovery in drug-free medium, biological properties and gene expression pattern were compared with those of the parental cell line. In a separate set of experiments, the effects of in vivo administration of imatinib to athymic nude (nu/nu) mice carrying MA-11 tumors were investigated. Results: In vitro, imatinib treatment increased the motility and invasiveness of the breast cancer cells, and induced over-expression of drug transporters and of a set of genes associated with aggressive and metastatic behavior (Table). In vivo, nu/nu mice subcutaneously implanted with MA-11 cells and treated with nine daily intraperitoneal doses of 60 mg/Kg imatinib developed with greater frequency distant organ metastases vs. control mice implanted with MA-11 and treated with the vehicle alone. Conclusions: Our data caution against the clinical use of imatinib in breast cancer; imatinib-selected breast cancer cells represent an important tool to investigate the pro-metastatic role of differentially expressed genes. [Table: see text] No significant financial relationships to disclose.

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A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells

Molecular Cancer Therapeutics ◽

10.1158/1535-7163.mct-06-0170 ◽

2006 ◽

Vol 5 (9) ◽

pp. 2300-2309 ◽

Cited By ~ 34

Author(s):

Alison J. Butt ◽

Caroline G. Roberts ◽

Alan A. Seawright ◽

Peter B. Oelrichs ◽

John K. MacLeod ◽

...

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Human Breast Cancer Cells ◽

Human Breast ◽

Plant Toxin

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Tumor lymphocytic infiltration, hormonal-metabolic status and aromatase gene expression in breast cancer

European Journal of Cancer ◽

10.1016/s0959-8049(97)84414-0 ◽

1997 ◽

Vol 33 ◽

pp. S10

Author(s):

L. Berstein ◽

T. Poroshina ◽

E. Tsyrtina ◽

V. Gamajunova ◽

O. Chernitsa ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Lymphocytic Infiltration ◽

Metabolic Status ◽

Aromatase Gene ◽

Aromatase Gene Expression

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The influence of efaproxiral on breast cancer xenograft hypoxia and HIF-1-alpha expression

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10102 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10102-10102

Author(s):

B. D. Kavanagh ◽

R. P. Steffen ◽

B. Frederick ◽

B. Solomon ◽

D. Chan

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Rna Extraction ◽

Tumor Oxygenation ◽

Human Breast ◽

Clinical Safety ◽

Early Effect ◽

Breast Cancer Xenograft ◽

Oxygen Breathing

10102 Background: Efaproxiral (E), a synthetic allosteric modifier of hemoglobin, has demonstrated clinical safety and efficacy as a radiosensitizer in patients with brain metastases from breast cancer. Although shown to enhance oxygenation in a murine mammary tumor, efaproxiral has not previously been tested in a human breast cancer xenograft. We studied changes in tumor oxygenation in a human xenograft and evaluated whether efaproxiral induces cell signaling events of potential therapeutic value. Methods: MDA-MB-468 breast cancer cells in matrigel were injected into the flank of nude mice. After tumors grew to 1–1.5 cm, animals were subjected to 1 of 3 treatments: ip saline +room air breathing (RA), ip saline + 50% oxygen breathing (O2), or ip efaproxiral (300 mg/kg) + 50% oxygen breathing (E+O2). Twenty minutes later the hypoxia marker, pimonidazole (pimo), was given, and 70 minutes later tumors were harvested for immunohistochemical study of hypoxia and hypoxia-inducible factor 1-alpha (HIF1-α) and RNA extraction to identify early changes in gene expression. Image analysis software was used to quantify observations. Results: Tumor hypoxia and HIF1-α staining were significantly decreased by efaproxiral (Table). HIF1-α staining did not entirely colocalize with pimo, implying different oxygen tension levels for HIF1-α ubiquitination and pimo reduction. Gene arrays indicated that after E+O2, expression of the hypoxia-induced DR1 transcription repressor was reduced compared with O2. Conclusions: The combination of E+O2 reduced hypoxia and HIF1-α expression in MDA-MB-468 human breast tumors in vivo, and an early effect on gene expression was reduced DR1. The results demonstrate an efaproxiral-mediated enhanced oxygenation of human hypoxic breast cancer. Furthermore, the efaproxiral-mediated down-regulation of HIF1-α suggests possible new opportunities in the clinical application of efaproxiral, notably as an adjuvant to systemic agents for which HIF1-α-mediated resistance limits efficacy. [Table: see text] [Table: see text]

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Human Breast Cancer Cells Are Redirected to Mammary Epithelial Cells upon Interaction with the Regenerating Mammary Gland Microenvironment In-Vivo

PLoS ONE ◽

10.1371/journal.pone.0049221 ◽

2012 ◽

Vol 7 (11) ◽

pp. e49221 ◽

Cited By ~ 24

Author(s):

Karen M. Bussard ◽

Gilbert H. Smith

Keyword(s):

Breast Cancer ◽

Mammary Gland ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Mammary Epithelial Cells ◽

Mammary Epithelial ◽

Human Breast Cancer Cells ◽

Human Breast

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Transcriptome analysis of heterogeneity in mouse model of metastatic breast cancer

Breast Cancer Research ◽

10.1186/s13058-021-01468-x ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Anastasia A. Ionkina ◽

Gabriela Balderrama-Gutierrez ◽

Krystian J. Ibanez ◽

Steve Huy D. Phan ◽

Angelique N. Cortez ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Metastatic Breast Cancer ◽

Mouse Model ◽

Cancer Cells ◽

Transcriptome Analysis ◽

Tumor Heterogeneity ◽

Cancer Metastasis ◽

Metastatic Breast ◽

Organ Tropism

Abstract Background Cancer metastasis is a complex process involving the spread of malignant cells from a primary tumor to distal organs. Understanding this cascade at a mechanistic level could provide critical new insights into the disease and potentially reveal new avenues for treatment. Transcriptome profiling of spontaneous cancer models is an attractive method to examine the dynamic changes accompanying tumor cell spread. However, such studies are complicated by the underlying heterogeneity of the cell types involved. The purpose of this study was to examine the transcriptomes of metastatic breast cancer cells using the well-established MMTV-PyMT mouse model. Methods Organ-derived metastatic cell lines were harvested from 10 female MMTV-PyMT mice. Cancer cells were isolated and sorted based on the expression of CD44low/EpCAMhigh or CD44high/EpCAMhigh surface markers. RNA from each cell line was extracted and sequenced using the NextSeq 500 Illumina platform. Tissue-specific genes were compared across the different metastatic and primary tumor samples. Reads were mapped to the mouse genome using STAR, and gene expression was quantified using RSEM. Single-cell RNA-seq (scRNA-seq) was performed on select samples using the ddSeq platform by BioRad and analyzed using Seurat v3.2.3. Monocle2 was used to infer pseudo-time progression. Results Comparison of RNA sequencing data across all cell populations produced distinct gene clusters. Differential gene expression patterns related to CD44 expression, organ tropism, and immunomodulatory signatures were observed. scRNA-seq identified expression profiles based on tissue-dependent niches and clonal heterogeneity. These cohorts of data were narrowed down to identify subsets of genes with high expression and known metastatic propensity. Dot plot analyses further revealed clusters expressing cancer stem cell and cancer dormancy markers. Changes in relevant genes were investigated across pseudo-time and tissue origin using Monocle2. These data revealed transcriptomes that may contribute to sub-clonal evolution and treatment evasion during cancer progression. Conclusions We performed a comprehensive transcriptome analysis of tumor heterogeneity and organ tropism during breast cancer metastasis. These data add to our understanding of metastatic progression and highlight targets for breast cancer treatment. These markers could also be used to image the impact of tumor heterogeneity on metastases.

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Quercetin Potentiates the Chemosensitivity of Human Breast Cancer Cells to 5-Fluorouracil

10.21203/rs.3.rs-682735/v1 ◽

2021 ◽

Author(s):

Fatemeh Mawalizadeh ◽

Ghorban Mohammadzadeh ◽

azam khedri ◽

mojtaba rashidi

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Colony Formation ◽

Breast Cancer Cells ◽

In Vivo Studies ◽

Mcf7 Cells ◽

Chemotherapy Drugs ◽

Apoptotic Effect

Abstract Background: breast cancer is one of the leading causes of cancer mortality worldwide. 5-fluorouracil (5-FU) is one of the chemotherapy drugs to treat breast cancer, but it is associated with several side effects. Combination therapy is a way to increase the effectiveness of chemo drugs and decrease their usage dose. Quercetin (Quer) is one of the natural polyphenols with anti-cancer properties. This study investigated the apoptotic effect of 5-FU in combination with Quer compared with 5-FU alone on MCF7 breast cancer cells.Method and Results: Different single and combined concentrations of 5-FU and Quer were applied to MCF 7 cells for 48 hours. Cell viability, apoptosis, gene expression of Bax and Bcl2, and colony number were assessed using MTT assay, flow cytometry, quantitative real-time PCR, and Colony formation assay, respectively. The combination of 5-FU and Quer compared to 5-FU alone improved apoptosis by increasing and decreasing the gene expression of Bax and Bcl2, respectively, and decreased colony formation in MCF7 cells.Conclusion: Quer potentiates the sensitivity of breast cancer to 5-FU so that this combination may be proposed as a treatment for breast cancer. Therefore, this combination can be suggested for future in vivo studies.

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