Functional and genomic characterization of a xenograft model system for the study of metastasis in triple-negative breast cancer
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PROVIDER: PRJNA437934 | ENA |
REPOSITORIES: ENA
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Project description:To define the molecular regulators of metastasis of triple-negative breast cancer, we conducted a rigorous characterization of four populations of MDA-MB-231 human triple-negative breast cancer cells that display a range of intrinsic spontaneous metastatic capacities in immuno-deficient mice, from non-metastatic to highly metastatic to lung, liver, spleen and spine. PAT-Seq gene expression profiling of primary tumor cells identified the fibroblast growth factor homologous factor, FGF13, as a candidate metastatic virulence gene highly upregulated in aggressively metastatic MDA-MB-231HM tumors.
2018-03-13 | GSE111705 | GEO
Project description:To define the molecular regulators of metastasis of triple-negative breast cancer, we conducted a rigorous characterization of four isogenic populations of MDA-MB-231 human triple-negative breast cancer cells that display a range of intrinsic spontaneous metastatic capacities in immuno-deficient mice, from non-metastatic to highly metastatic to lung, liver, spleen and spine. PAT-Seq gene expression profiling of primary tumor cells identified the fibroblast growth factor homologous factor, FGF13, as a candidate metastatic virulence gene highly upregulated in aggressively metastatic MDA-MB-231HM tumors.
2018-02-01 | GSE101745 | GEO
Project description:Metastasis in triple-negative breast cancer
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Project description:Triple therapy reduced metastasis in triple-negative breast cancer.
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Project description:This microarray dataset contains 51 triple-negative breast cancers with clinical and recurrence information for at least 3 years of follow-up and 106 luminal breast cancers (reanalyzed data from Series GSE24124, GSE9309, and GSE17040). A novel set of 45-gene signature that was statistically predictive of distant metastasis recurrence for triple-negative breast cancer was identified in this study.
2012-11-01 | GSE33926 | GEO
Project description:Triple negative breast cancer (TNBC) is an aggressive subtype that lack targeted clinical therapies. In addition, TNBC is heterogeneous and was recently further sub-classified into seven TNBC subtypes that displayed unique gene expression patterns. To develop therapeutic treatment regimens, we established seven patient-derived xenograft models from TNBC tumors. These xenograft models not only retained the histology and clinical markers of the corresponding patient tumors, but also bearing the same mutations and deletions identified in the patient tumors. Moreover, as part of evaluation of these models, we performed microarrays on the xenograft tumors to assess their TNBC subtypes. After obtaining IRB-approved informed written patient consent, breast cancer tissues were obtained fresh from Stanford Hospital and transplanted into the number 2 mammary fat pads of female NOD SCID mice (NOD.CB17-Prkdcscid/J, Jackson Laboratory West, Sacramento, CA, USA). Mice were maintained in pathogen-free animal housing. The established xenografts were subsequently passaged from mouse to mouse. Xenograft tumor tissues were frozen on dry ice for RNA isolation and microarray analysis.
2014-03-21 | E-GEOD-47079 | biostudies-arrayexpress
Project description:Aberrant SMAD3 activation has been implicated as a driving event in cancer metastasis. However, the drivers of SMAD3 activation are poorly defined. Here, we identify SMAD3 as a non-histone substrate of lysine acetyltransferase 6A (KAT6A). The acetylation of SMAD3 at K20 and K117 by KAT6A with promotes SMAD3 association with oncogenic H3K23ac reader TRIM24 and upregulation of immune response-related cytokines. This event in turn leads to enhanced myeloid-derived suppressor cell (MDSC) recruitment and triple-negative breast cancer (TNBC) metastasis. Inhibiting KAT6A in combination with anti-PD-L1 therapy in treating breast cancer xenograft-bearing animals markedly attenuates TNBC metastasis and provides a significant survival benefit. Thus, our work presents an KAT6A acetylation-dependent regulatory mechanism governing SMAD3 oncogenic function and provides insight into how targeting an epigenetic factor with immunotherapies enhances the anti-metastasis efficacy.
2021-11-03 | GSE171230 | GEO
Project description:Triple negative breast cancer (TNBC) is an aggressive subtype that lack targeted clinical therapies. In addition, TNBC is heterogeneous and was recently further sub-classified into seven TNBC subtypes that displayed unique gene expression patterns. To develop therapeutic treatment regimens, we established seven patient-derived xenograft models from TNBC tumors. These xenograft models not only retained the histology and clinical markers of the corresponding patient tumors, but also bearing the same mutations and deletions identified in the patient tumors. Moreover, as part of evaluation of these models, we performed microarrays on the xenograft tumors to assess their TNBC subtypes.
2014-03-21 | GSE47079 | GEO
Project description:Gene Expression Profiling of a Mouse Xenograft Model of “Triple-Negative” Breast Cancer Brain Metastases With and Without Vorinostat Treatment. Purpose: As chemotherapy and molecular therapy improve the systemic survival of breast cancer patients, the incidence of brain metastases increases. Few therapeutic strategies exist for the treatment of brain metastases because the blood-brain barrier severely limits drug access. We report the pharmacokinetic, efficacy, and mechanism of action studies for the histone deactylase inhibitor vorinostat (suberoylanilide hydroxamic acid) in a preclinical model of brain metastasis of triple-negative breast cancer. Experimental Design: The 231-BR brain trophic subline of the MDA-MB-231 human breast cancer cell line was injected into immunocompromised mice for pharmacokinetic and metastasis studies. Pharmacodynamic studies compared histone acetylation, apoptosis, proliferation, and DNA damage in vitro and in vivo. Results: Following systemic administration, uptake of [14C]vorinostat was significant into normal rodent brain and accumulation was up to 3-fold higher in a proportion of metastases formed by 231-BR cells. Vorinostat prevented the development of 231-BR micrometastases by 28% (P = 0.017) and large metastases by 62% (P < 0.0001) compared with vehicle-treated mice when treatment was initiated on day 3 post-injection. The inhibitory activity of vorinostat as a single agent was linked to a novel function in vivo: induction of DNA double-strand breaks associated with the down-regulation of the DNA repair gene Rad52. Conclusions: We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation.
2009-10-14 | GSE18544 | GEO
Project description:NAD+ levels decline with age and in certain disease conditions. NAD+ precursors have been shown to stimulate NAD+ biosynthesis and ameliorate various age-associated diseases in mouse models. However, NAD+ metabolism is complicated in cancer and its role in triple-negative breast cancer (TNBC) remains elusive. Here, we show that NAD+ supplement suppresses tumor metastasis in a TNBC orthotopic patient-derived xenograft (PDX) model. Sirtuin1 lysine deacetylase (SIRT1) is required for the effects since SIRT1 knockdown blocks NAD+-suppressed tumor metastasis. Overexpression of SIRT1 effectively impairs the metastatic potential of TNBC. Importantly, the interaction between SIRT1 and p66Shc causes the deacetylation and functional inactivation of p66Shc, which inhibits epithelial-mesenchymal transition (EMT). Overall, we demonstrate that NAD+ supplementation executes its anti-tumor function via activating the SIRT1-p66Shc axis, which highlights the preventive and therapeutic potential of SIRT1 activators as effective interventions for TNBC.
2023-01-23 | GSE220683 | GEO