Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells

The pituitary hormone prolactin (PRL) plays an important role in mammary gland development. It was also suggested to contribute to breast cancer progression. In vivo data strongly supported a crucial role of PRL in promoting tumour growth; however, PRL demonstrated only a weak, if any, pro-proliferative effect on cancer cells in vitro. Several recent studies indicated that PRL action in vivo may be influenced by the hormonal milieu, e.g. other growth factors such as 17β-oestradiol (E2). Here, we explored the potential interplay between PRL and E2 in regulation of gene expression and cell growth. PRL alone induced either a weak or no proliferative response of T47D and BT-483 cells respectively, while it drastically enhanced cell proliferation in E2-stimulated cultures. Affymetrix microarray analysis revealed 12 genes to be regulated by E2, while 57 genes were regulated by PRL in T47D cells. Most of the PRL-regulated genes (42/57) were not previously described as PRL target genes, e.g. WT1 and IER3. One hundred and five genes were found to be regulated upon PRL/E2 co-treatment: highest up-regulation was found for EGR3, RUNX2, EGR1, MAFF, GLIPR1, IER3, SOCS3, WT1 and AREG. PRL and E2 synergised to regulate EGR3, while multiple genes were regulated additively. These data show a novel interplay between PRL and E2 to modulate gene regulation in breast cancer cells.

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Imatinib-induced changes in gene expression and the metastatic potential of human breast carcinoma cells

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.1074 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 1074-1074

Author(s):

A. Lorico ◽

F. Anzanello ◽

G. Rappa

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Breast Carcinoma ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Carcinoma Cells ◽

Myelogenous Leukemia ◽

Breast Carcinoma Cells

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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Arctigenin Attenuates Breast Cancer Progression through Decreasing GM-CSF/TSLP/STAT3/β-Catenin Signaling

International Journal of Molecular Sciences ◽

10.3390/ijms21176357 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6357

Author(s):

Hui Shi ◽

Luping Zhao ◽

Xinlin Guo ◽

Runping Fang ◽

Hui Zhang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Nuclear Translocation ◽

Breast Cancer Progression ◽

Gm Csf ◽

Stat3 Phosphorylation

Invasive breast cancer is highly regulated by tumor-derived cytokines in tumor microenvironment. The development of drugs that specifically target cytokines are promising in breast cancer treatment. In this study, we reported that arctigenin, a bioactive compound from Arctium lappa L., could decrease tumor-promoting cytokines GM-CSF, MMP-3, MMP-9 and TSLP in breast cancer cells. Arctigenin not only inhibited the proliferation, but also the invasion and stemness of breast cancer cells via decreasing GM-CSF and TSLP. Mechanistically, arctigenin decreased the promoter activities of GM-CSF and TSLP via reducing the nuclear translocation of NF-κB p65 which is crucial for the transcription of GM-CSF and TSLP. Furthermore, arctigenin-induced depletion of GM-CSF and TSLP inhibited STAT3 phosphorylation and β-catenin signaling resulting in decreased proliferation, invasion and stemness of breast cancer cells in vitro and in vivo. Our findings provide new insights into the mechanism by which tumor-promoting cytokines regulate breast cancer progression and suggest that arctigenin is a promising candidate for cytokine-targeted breast cancer therapy.

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MicroRNA-374b inhibits breast cancer progression through regulating CCND1 and TGFA genes

Carcinogenesis ◽

10.1093/carcin/bgab005 ◽

2021 ◽

Author(s):

Yan Liu ◽

Ai Zhang ◽

Ping-Ping Bao ◽

Li Lin ◽

Yina Wang ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Molecular Mechanisms ◽

Breast Cancer Progression ◽

Breast Cancer Cell Lines ◽

Malignant Behavior

Abstract Emerging evidence indicates that microRNAs (miRNAs) play a critical role in breast cancer development. We recently reported that a higher expression of miR-374b in tumor tissues was associated with a better disease-free survival of triple-negative breast cancer (TNBC). However, the functional significance and molecular mechanisms underlying the role of miR-374b in breast cancer are largely unknown. In this current study, we evaluated the biological functions and potential mechanisms of miR-374b in both TNBC and non-TNBC. We found that miR-374b was significantly downregulated in breast cancer tissues, compared to adjacent tissues. MiR-374b levels were also lower in breast cancer cell lines, as compared to breast epithelial cells. In vitro and in vivo studies demonstrated that miR-374b modulates the malignant behavior of breast cancer cells, such as cell proliferation in 2D and 3D, cell invasion ability, colony forming ability, and tumor growth in mice. By using bioinformatics tools, we predicted that miR-374b plays a role in breast cancer cells through negatively regulating cyclin D1 (CCND1) and transforming growth factor alpha (TGFA). We further confirmed that CCND1 and TGFA contribute to the malignant behavior of breast cancer cells in vitro and in vivo. Our rescue experiments showed that overexpressing CCND1 or TGFA reverses the phenotypes caused by miR-374b overexpression. Taken together, our studies suggest that miR-374b modulates malignant behavior of breast cancer cells by negatively regulating CCND1 and TGFA genes. The newly identified miR-374b-mediated CCND1 and TGFA gene silencing may facilitate a better understanding of the molecular mechanisms of breast cancer progression.

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Osterix Decreases the Chemosensitivity of Breast Cancer Cells by Upregulating GALNT14

Cellular Physiology and Biochemistry ◽

10.1159/000485400 ◽

2017 ◽

Vol 44 (3) ◽

pp. 998-1010 ◽

Cited By ~ 3

Author(s):

Jiahui Wu ◽

Xiang Chen ◽

Qianyi Bao ◽

Rui Duan ◽

Yucui Jin ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Target Genes ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Elevated Expression ◽

Hoechst Staining

Background/Aims: Osterix (Osx), a key regulator of osteoblast differentiation and bone formation, has been recently reported to be associated with the progression of breast cancer. However, the precise roles of Osx in breast cancer remain unclear. Methods: Drug sensitivity of the cancer cells was assessed using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Target genes were obtained by high-throughput Illumina sequencing and were confirmed in vitro and in vivo. Apoptosis was analysed by Hoechst staining and western blotting. A tissue microarray including 129 samples from breast cancer patients was used for immunohistochemistry (IHC) assays. Results: Overexpression of Osx decreased the chemosensitivity of breast cancer cells, while knockdown of Osx increased the chemosensitivity of breast cancer cells. In particular, we found that the decreased chemosensitivity effect was significantly associated with elevated expression of the polypeptide N-acetylgalactosaminyltransferase 14 (GALNT14). Silencing of GALNT14 in Osx-overexpressed cells restored the decreased chemosensitivity. Conversely, overexpression of GALNT14 in Osx-knockdown cells abrogated the increased chemosensitivity in breast cancer cells. In addition, we revealed that Osx decreased GALNT14-dependent chemosensitivity by enhancing anti-apoptosis. GALNT14 expression exhibited a significant association with breast cancer stages as well as the disease-free survival (DFS) rate. Conclusion: Osx plays an important role in the chemosensitivity and inhibition of Osx expression may represent a therapeutic strategy to enhance the chemosensitivity of breast cancer.

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Parvin-β Inhibits Breast Cancer Tumorigenicity and Promotes CDK9-Mediated Peroxisome Proliferator-Activated Receptor Gamma 1 Phosphorylation

Molecular and Cellular Biology ◽

10.1128/mcb.01617-06 ◽

2007 ◽

Vol 28 (2) ◽

pp. 687-704 ◽

Cited By ~ 29

Author(s):

Cameron N. Johnstone ◽

Perry S. Mongroo ◽

A. Sophie Rich ◽

Michael Schupp ◽

Mark J. Bowser ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Three Dimensional ◽

Nuclear Hormone Receptor ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor

ABSTRACT Parvin-β is a focal adhesion protein downregulated in human breast cancer cells. Loss of Parvin-β contributes to increased integrin-linked kinase activity, cell-matrix adhesion, and invasion through the extracellular matrix in vitro. The effect of ectopic Parvin-β expression on the transcriptional profile of MDA-MB-231 breast cancer cells, which normally do not express Parvin-β, was evaluated. Particular emphasis was placed upon propagating MDA-MB-231 breast cancer cells in three-dimensional culture matrices. Interestingly, Parvin-β reexpression in MDA-MB-231 cells increased the mRNA expression, serine 82 phosphorylation (mediated by CDK9), and activity of the nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ), and there was a concomitant increase in lipogenic gene expression as a downstream effector of PPARγ. Importantly, Parvin-β suppressed breast cancer growth in vivo, with associated decreased proliferation. These data suggest that Parvin-β might influence breast cancer progression.

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Cytoplasmic ATXN7L3B Interferes with Nuclear Functions of the SAGA Deubiquitinase Module

Molecular and Cellular Biology ◽

10.1128/mcb.00193-16 ◽

2016 ◽

Vol 36 (22) ◽

pp. 2855-2866 ◽

Cited By ~ 10

Author(s):

Wenqian Li ◽

Boyko S. Atanassov ◽

Xianjiang Lan ◽

Ryan D. Mohan ◽

Selene K. Swanson ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Target Genes ◽

Histone Acetyltransferase ◽

Adaptor Proteins ◽

Catalytic Subunit ◽

Saga Complex

The SAGA complex contains two enzymatic modules, which house histone acetyltransferase (HAT) and deubiquitinase (DUB) activities. USP22 is the catalytic subunit of the DUB module, but two adaptor proteins, ATXN7L3 and ENY2, are necessary for DUB activity toward histone H2Bub1 and other substrates. ATXN7L3B shares 74% identity with the N-terminal region of ATXN7L3, but the functions of ATXN7L3B are not known. Here we report that ATXN7L3B interacts with ENY2 but not other SAGA components. Even though ATXN7L3B localizes in the cytoplasm, ATXN7L3B overexpression increases H2Bub1 levels, while overexpression of ATXN7L3 decreases H2Bub1 levels. In vitro , ATXN7L3B competes with ATXN7L3 to bind ENY2, and in vivo , knockdown of ATXN7L3B leads to concomitant loss of ENY2. Unlike the ATXN7L3 DUB complex, a USP22-ATXN7L3B-ENY2 complex cannot deubiquitinate H2Bub1 efficiently in vitro . Moreover, ATXN7L3B knockdown inhibits migration of breast cancer cells in vitro and limits expression of ER target genes. Collectively, our studies suggest that ATXN7L3B regulates H2Bub1 levels and SAGA DUB activity through competition for ENY2 binding.

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Enhanced Gene Expression in Breast Cancer Cells in Vitro and Tumors in Vivo

Molecular Therapy ◽

10.1006/mthe.2002.0813 ◽

2002 ◽

Vol 6 (6) ◽

pp. 783-792 ◽

Cited By ~ 28

Author(s):

Huanzhang Lu ◽

Yufeng Zhang ◽

David D. Roberts ◽

C.Kent Osborne ◽

Nancy Smyth Templeton

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Breast Cancer Cells

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Urtica dioica Extract Inhibits Proliferation and Induces Apoptosis and Related Gene Expression of Breast Cancer Cells In Vitro and In Vivo

Clinical Breast Cancer ◽

10.1016/j.clbc.2017.04.008 ◽

2017 ◽

Vol 17 (6) ◽

pp. 463-470 ◽

Cited By ~ 5

Author(s):

Ali Mohammadi ◽

Behzad Mansoori ◽

Pooneh Chokhachi Baradaran ◽

Vahid Khaze ◽

Mahyar Aghapour ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Urtica Dioica ◽

Related Gene

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The antihyperlipidemic drug Potassium Piperate impairs migration and tumorgenesis of breast cancer cells via upregulation of miR-31

10.21203/rs.3.rs-290044/v1 ◽

2021 ◽

Author(s):

Junping Lu ◽

Xiaoxia Tian ◽

Mailisu Mailisu ◽

Morigen Morigen ◽

Lifei Fan

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Cell ◽

Cell Invasion ◽

Combination Treatment ◽

Breast Cancer Cells ◽

Target Genes ◽

Cancer Cell Invasion

Abstract Background Breast cancer is a leading malignant tumor which causes deaths among women, and metastasis is the primary cause for mortality in breast cancer. Due to the involvement of many regulatory molecules and signaling pathways, the occurrence and development process of metastasis needs to be further studied. MicroRNAs (miRNAs) are ubiquitously expressed small non-coding RNAs that have been shown to play an important role in the diagnosis and treatment of many diseases, as well as constituting an attractive candidate to control metastasis. In this study, we tried to uncover the mechanism of GBK in impairing breast cancer cell invasion and metastasis.Methods We treated cancer cells with GBK or not, found its target miRNA by analyzed miRNA transcriptional changes and the miRNA target genes by performed with the QT-PCR and Western Blot. The proliferation of breast cancer cells in vitro and in vivo under combination treatment with GBK and DDP was measured by CCK-8 kit and the nude mice tumor formation experiment.Results We found tumor suppressor miR-31 was a main target of GBK. GBK treatment affected the epigenetic modification at CpG sites by downregulating DNA methyltransferases, thus the methylation levels at CpG of lncRNA LOC554202 decreased significantly, and in turn upregulating of both miR-31 and its host gene LOC554202 in breast cancer cells. We also observed significant inhibition of miR-31 target genes under GBK stimulation, including RhoA, WAVE3 and SATB2, which all closely related to cancer cell invasion, migration and proliferation. Furthermore, we revealed that combination treatment with GBK and DDP had synergistic and dose reduction potential in inhibiting the proliferation of breast cancer cells in vitro and in vivo, especially in TNBC.Conclusion This study further analyzes the target and underlying mechanism of GBK in inhibiting breast cancer migration and invasion, and provides theoretical support for the development of GBK as an auxiliary drug for clinical treatment.

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The deubiquitinating enzyme USP15 stabilizes ERα and promotes breast cancer progression

Cell Death and Disease ◽

10.1038/s41419-021-03607-w ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Xiaohong Xia ◽

Chuyi Huang ◽

Yuning Liao ◽

Yuan Liu ◽

Jinchan He ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Cells ◽

Cancer Progression ◽

Breast Cancer Cells ◽

Estrogen Receptor Α ◽

Breast Cancer Progression ◽

Breast Cancers ◽

Incidence And Mortality

AbstractBreast cancer has the highest incidence and mortality in women worldwide. There are 70% of breast cancers considered as estrogen receptor α (ERα) positive. Therefore, the ERα-targeted therapy has become one of the most effective solution for patients with breast cancer. Whereas a better understanding of ERα regulation is critical to shape evolutional treatments for breast cancer. By exploring the regulatory mechanisms of ERα at levels of post-translational modifications, we identified the deubiquitinase USP15 as a novel protector for preventing ERα degradation and a critical driver for breast cancer progression. Specifically, we demonstrated that USP15 promoted the proliferation of ERα+, but not ERα- breast cancer, in vivo and in vitro. Meanwhile, USP15 knockdown notably enhanced the antitumor activities of tamoxifen on breast cancer cells. Importantly, USP15 knockdown induced the downregulation of ERα protein via promoting its K48-linked ubiquitination, which is required for proliferative inhibition of breast cancer cells. These findings not only provide a novel treatment for overcoming resistance to endocrine therapy, but also represent a therapeutic strategy on ERα degradation by targeting USP15-ERα axis.

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