scholarly journals Bone morphogenetic protein 6 (BMP6) and BMP7 inhibit estrogen-induced proliferation of breast cancer cells by suppressing p38 mitogen-activated protein kinase activation

2008 ◽  
Vol 199 (3) ◽  
pp. 445-455 ◽  
Author(s):  
Mina Takahashi ◽  
Fumio Otsuka ◽  
Tomoko Miyoshi ◽  
Hiroyuki Otani ◽  
Junko Goto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Steroid Sulfatase ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cell Mitosis ◽  
Mcf 7

Estrogen is involved in the development and progression of breast cancer. Here, we investigated the effects of bone morphogenetic proteins (BMPs) on breast cancer cell proliferation caused by estrogen using human breast cancer MCF-7 cells. MCF-7 cells express estrogen receptors (ESR1 and ESR2), BMP receptors, and SMAD signaling molecules. Estradiol and membrane-impermeable estradiol stimulated MCF-7 cell proliferation. Estradiol also reduced mRNA levels of ESR1, aromatase, and steroid sulfatase. Treatment with BMPs and activin had no effects on MCF-7 cell proliferation. However, BMP2, BMP4, BMP6, BMP7, and activin suppressed estradiol-induced cell mitosis, with the effects of BMP6, BMP7, and activin being more prominent than those of BMP2 and BMP4. Activin decreased ESR1 mRNA expression, while BMP6 and BMP7 impaired steroid sulfatase expression in MCF-7 cells. Interestingly, SMAD1,5,8 activation elicited by BMP6 and BMP7, but not by BMP2 and BMP4, was preserved even under the exposure of a high concentration of estradiol. The difference of BMP responsiveness was likely due to the differential modulation of BMP receptor expression induced by estradiol. In this regard, estradiol decreased the expression levels of BMPR1A, BMPR1B, ACVR2A, and ACVR2B but did not affect ACVR1 and BMPRII, leading to the sustained effects of BMP6 and BMP7 in estrogen-treated MCF-7 cells. Estradiol rapidly activated MAPK phosphorylation including extracellular signal-regulated kinase 1/2, p38, and stress-activated protein kinase/c-Jun NH2-terminal kinase pathways and BMP6, BMP7, and activin preferentially inhibited estradiol-induced p38 phosphorylation. SB203580, a selective p38 MAPK inhibitor effectively suppressed estradiol-induced cell mitosis, suggesting that p38 MAPK plays a key role in estrogen-sensitive breast cancer cell proliferation. Thus, a novel interrelationship between estrogen and the breast cancer BMP system was uncovered, in which inhibitory effects of BMP6 and BMP7 on p38 signaling and steroid sulfatase expression were functionally involved in the suppression of estrogen-induced mitosis of breast cancer cells.

ILF3-AS1 promotes cell proliferation and inhibits cell apoptosis of breast cancer by binding with miR-4429 to upregulate RAB14

2021 ◽  
pp. 096032712198942
Author(s):  
Xiaoxue Zhang ◽  
Xianxin Xie ◽  
Kuiran Gao ◽  
Xiaoming Wu ◽  
Yanwei Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Breast Cancer Cell ◽  
Cell Apoptosis ◽  
Breast Cancer Cells ◽  
Migration And Invasion ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Cancer Tissues

As one of the leading causes of cancer-related deaths among women, breast cancer accounts for a 30% increase of incidence worldwide since 1970s. Recently, increasing studies have revealed that the long non-coding RNA ILF3-AS1 is involved in the progression of various cancers. Nevertheless, the role of ILF3-AS1 in breast cancer remains largely unknown. In the present study, we found that ILF3-AS1 was highly expressed in breast cancer tissues and cells. ILF3-AS1 silencing inhibited breast cancer cell proliferation, migration and invasion, and promoted cell apoptosis. ILF3-AS1 bound with miR-4429 in breast cancer cells. Moreover, RAB14 was a downstream target of miR-4429, and miR-4429 expression was negatively correlated with RAB14 or ILF3-AS1 expression in breast cancer tissues. The result of rescue experiments demonstrated that overexpression of RAB14 can reverse the inhibitory effect of ILF3-AS1 knockdown on breast cancer cell proliferation, migration and invasion. Overall, ILF3-AS1 promotes the malignant phenotypes of breast cancer cells by interacting with miR-4429 to regulate RAB14, which might offer a new insight into the underlying mechanism of breast cancer.

scholarly journals Aryl Hydrocarbon Receptor Ligands Inhibit IGF-II and Adipokine Stimulated Breast Cancer Cell Proliferation

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Travis B. Salisbury ◽  
Gary Z. Morris ◽  
Justin K. Tomblin ◽  
Ateeq R. Chaudhry ◽  
Carla R. Cook ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Aryl Hydrocarbon

Obesity increases human cancer risk and the risk for cancer recurrence. Adipocytes secrete paracrine factors termed adipokines that stimulate signaling in cancer cells that induce proliferation. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that plays roles in tumorigenesis, is regulated by exogenous lipophilic chemicals, and has been explored as a therapeutic target for cancer therapy. Whether exogenous AHR ligands modulate adipokine stimulated breast cancer cell proliferation has not been investigated. We provide evidence that adipocytes secrete insulin-like growth factor 2 (IGF-2) at levels that stimulate the proliferation of human estrogen receptor (ER) positive breast cancer cells. Using highly specific AHR ligands and AHR short interfering RNA (AHR-siRNA), we show that specific ligand-activated AHR inhibits adipocyte secretome and IGF-2-stimulated breast cancer cell proliferation. We also report that a highly specific AHR agonist significantly (P<0.05) inhibits the expression of E2F1, CCND1 (known as Cyclin D1), MYB, SRC, JAK2, and JUND in breast cancer cells. Collectively, these data suggest that drugs that target the AHR may be useful for treating cancer in human obesity.

scholarly journals Alternative MyD88 -Cyclin D1 signaling in breast cancer cells regulates TLR3 mediated cell proliferation

2020 ◽  
Author(s):  
Aradhana Singh ◽  
Ranjitsinh Devkar ◽  
Anupam Basu
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Adjuvant Therapy ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Surface Localization ◽  
Tlr3 Signaling

AbstractTLR3 mediated apoptotic changes in cancer cells are well documented and hence several synthetic ligands of TLR3 are being used for adjuvant therapy. But there are reports showing contradictory effect of TLR3 signaling which includes our previous report that had shown cell proliferation following surface localization of TLR 3. However, the underlying mechanism of cell surface localization of TLR3 and subsequent cell proliferation lacks clarity. This study addresses TLR3 ligand mediated signaling cascade that regulates a proliferative effect in breast cancer cells (MDA MB 231 and T47D) challenged with TLR3 ligand in the presence of MyD88 inhibitor. Evidences were obtained using immunoblotting, co-immunoprecipitation, confocal microscopy, Immunocytochemistry, ELISA, and flowcytometry. Results had revealed that TLR3 ligand treatment significantly enhanced breast cancer cell proliferation marked by an upregulated expression of cyclinD1 but the same were suppressed by addition of MyD88 inhibitor. Also, expression of IRAK1-TRAF6-TAK1 were altered in the given TLR3-signaling pathway. Inhibition of MyD88 disrupted the downstream adaptor complex and mediated signaling through TLR3-MyD88-NF-κB (p65)-IL6-Cyclin D1 pathway. TLR3 mediated alternative signaling of the TLR3-MyD88-IRAK1-TRAF6-TAK1-TAB1-NF-κB axis leads to upregulation of IL6 and cyclinD1. This response is hypothesized to be via the MyD88 gateway that culminates in proliferation of breast cancer cells. Overall, this study provides first comprehensive evidence on involvement of canonical signaling of TLR3 using MyD88 - Cyclin D1 mediated breast cancer cell proliferation. The findings elucidated herein will provide valuable insights into understand the TLR3 mediated adjuvant therapy in cancer.

scholarly journals Integrin αvβ3 in the Mediating Effects of Dihydrotestosterone and Resveratrol on Breast Cancer Cell Proliferation

2020 ◽  
Vol 21 (8) ◽  
pp. 2906
Author(s):  
Yih Ho ◽  
Zi-Lin Li ◽  
Ya-Jung Shih ◽  
Yi-Ru Chen ◽  
Kuan Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Plasma Membrane ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Integrin Αvβ3 ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation

Hormones and their receptors play an important role in the development and progression of breast cancer. Hormones regulate the proliferation of breast cancer cells through binding between estrogen or progestins and steroid receptors that may reside in the cytoplasm or be transcriptionally activated as steroid–protein nuclear receptor complexes. However, receptors for nonpeptide hormones also exist in the plasma membrane. Via those receptors, hormones are able to stimulate breast cancer cell proliferation when activated. Integrins are heterodimeric structural proteins of the plasma membrane. Their primary functions are to interact with extracellular matrix proteins and growth factors. Recently, integrin αvβ3 has been identified as a receptor for nonpeptide hormones, such as thyroid hormone and dihydrotestosterone (DHT). DHT promotes the proliferation of human breast cancer cells through binding to integrin αvβ3. A receptor for resveratrol, a polyphenol stilbene, also exists on this integrin in breast cancer cells, mediating the anti-proliferative, pro-apoptotic action of the compound in these cells. Unrelated activities of DHT and resveratrol that originate at integrin depend upon downstream stimulation of mitogen-activated protein kinase (MAPK, ERK1/2) activity, suggesting the existence of distinct, function-specific pools of ERK1/2 within the cell. This review will discuss the features of these receptors in breast cancer cells, in turn suggesting clinical applications that are based on the interactions of resveratrol/DHT with integrin αvβ3 and other androgen receptors.

scholarly journals Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fengqin Shi ◽  
Ya Li ◽  
Rui Han ◽  
Alan Fu ◽  
Ronghua Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Epigenetic Modifications ◽  
Valeric Acid ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation

AbstractValerian root (Valeriana officinalis) is a popular and widely available herbal supplement used to treat sleeping disorders and insomnia. The herb’s ability to ameliorate sleep dysfunction may signify an unexplored anti-tumorigenic effect due to the connection between circadian factors and tumorigenesis. Of particular interest are the structural similarities shared between valeric acid, valerian's active chemical ingredient, and certain histone deacteylase (HDAC) inhibitors, which imply that valerian may play a role in epigenetic gene regulation. In this study, we tested the hypothesis that the circadian-related herb valerian can inhibit breast cancer cell growth and explored epigenetic changes associated with valeric acid treatment. Our results showed that aqueous valerian extract reduced growth of breast cancer cells. In addition, treatment of valeric acid was associated with decreased breast cancer cell proliferation, migration, colony formation and 3D formation in vitro in a dose- and time-dependent manner, as well as reduced HDAC activity and a global DNA hypomethylation. Overall, these findings demonstrate that valeric acid can decrease the breast cancer cell proliferation possibly by mediating epigenetic modifications such as the inhibition of histone deacetylases and alterations of DNA methylation. This study highlights a potential utility of valeric acid as a novel HDAC inhibitor and a therapeutic agent in the treatment of breast cancer.

scholarly journals GLUTATHIONE AND GLUTAREDOXIN IN ROSCOVITINE-MEDIATED INHIBITION OF BREAST CANCER CELL PROLIFERATION

2017 ◽  
Vol 72 (4) ◽  
pp. 261-267 ◽  
Author(s):  
E. V. Shakhristova ◽  
E. A. Stepovaya ◽  
O. L. Nosareva ◽  
E. V. Rudikov ◽  
V. V. Novitsky
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Breast Cancer Cell ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Mcf 7

Background: Breast tumors are number one cause of cancer morbidity and mortality among women around the world, and Russia is not an exception. Many proteins that control proliferation of immortalized cells are redox-regulated, which is essential for modulating cellular proliferative activity, especially during tumor growth. Studying the role of glutaredoxin and glutathione in cell cycle phase distribution will allow not only to identify the molecular targets regulating cell proliferation, but also to develop methods of diagnosis and targeted therapy of socially sensitive diseases, including breast cancer, in the future.Aims: To evaluate the role of glutathione and glutaredoxin in the molecular mechanisms regulating MCF-7 breast cancer cell proliferation under the effects of roscovitine, a cyclin-dependent protein kinase inhibitor.Materials and methods: The MCF-7 cell line (human breast adenocarcinoma) was used in the study. The cell culture was incubated in the presence and absence of roscovitine in the final concentration of 20 µmol for 18 h. The production of reactive oxygen species, the distribution of cells between cell cycle phases and the amount of Annexin V positive cells were determined using flow cytometry. The concentrations of total, reduced and oxidized glutathione, protein SH groups and protein-bound glutathione were measured by spectrophotometry. The levels of glutaredoxin, cyclin E and cyclin-dependent protein kinases were estimated by Western blotting with monoclonal antibodies.Results: The effects of roscovitine in the MCF-7 cells resulted in cell cycle arrest in G2/М phases with the decreased levels of cyclin E and cyclin-dependent protein kinase 2. It was accompanied by activation of programmed cell death. In tumor cells incubated in the presence of roscovitine, oxidative stress was triggered, which was accompanied by the elevated generation of reactive oxygen species, the decrease in the concentration of reduced glutathione, and the rise in the level of glutaredoxin. It contributed to the increase in protein glutathionylation against the backdrop of the decreased SH group concentration.Conclusions: Breast cancer cell proliferation under the effects of roscovitine is reduced following not only the decrease in the cyclin level and cyclin-dependent protein kinase activity, but also the shift in the intracellular oxidant/antioxidant ratio. Roscovitine-induced oxidative stress in the MCF-7 cells contributed to protein glutathionylation with the changes in the protein structure and functions. It results in impaired cell cycle progression, indicating a possibility to regulate cellular proliferation through modulating functional properties of redox-dependent proteins using the glutathione/glutaredoxin system.

scholarly journals FAM96A and FAM96B Suppress Breast Cancer Proliferation and Migration via the Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Di-Di Zhang ◽  
Xiao-Lin Sun ◽  
Zhao-Yuan Liang ◽  
Li-Na Zhang
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cancer Progression ◽  
Breast Cancer Cells ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Cell Proliferation ◽  
Invasion And Migration ◽  
And Migration

Abstract Background: Family with sequence similarity 96 member A and B (FAM96A and FAM96B) are two highly conserved homologous proteins belonging to MIP18 family. Many studies have shown that FAM96A and FAM96B play many different functions mainly through interacting with other different proteins. Recently, several studies show that FAM96A and FAM96B are significantly down-regulated compared in human gastrointestinal stromal tumors, colon cancer, liver cancer and gastric cancer with corresponding normal tissues. However, the molecular regulatory mechanisms of FAM96A and FAM96B in breast cancer development and metastasis are still unclear. In this work, we aimed to explore the molecular mechanisms of FAM96A and FAM96B in breast cancer progression.Methods: We used specific siRNAs to down-regulate FAM96A and FAM96B expression, and used recombinant plasmids to up-regulate FAM96A and FAM96B expression in breast cancer cells. Cell proliferation was measured using MTT and colony formation assays. Cell cycle and apoptosis were detected by flow cytometry analysis. Wound healing and transwell assays were used to examine cell migration and invasion abilities. The relationships among FAM96A/B, EMT and Wnt/β-catenin signaling pathway were determined by analyzing the expression changes of classical markers and biological functional changes after XAV-939 inhibitor treatment. Results: We found that FAM96A and FAM96B expression in breast cancer was down-regulated. FAM96A/B overexpression suppressed breast cancer cell proliferation, invasion and migration, induced cell apoptosis and led to cell cycle arrested in G0/G1 phase. Conversely, FAM96A/B knockdown exhibited the opposite effects on breast cancer cells. Moreover, our data demonstrated that FAM96A/B overexpression suppressed EMT and Wnt/β-catenin signaling pathway, while FAM96A/B knockdown showed the promoting effects on EMT and Wnt/β-catenin signaling pathway in breast cancer cells. Furthermore, a Wnt pathway inhibitor, XAV-939 treatment reversed the promoting effects of FAM96A and FAM96B knockdown on breast cancer cell proliferation, invasion and migration.Conclusions: Our findings revealed that FAM96A and FAM96B may act as tumor suppressor genes and inhibit breast cancer progression via modulating the Wnt/β-catenin pathway, which can provide the potential markers for the diagnosis and treatment of breast cancer.

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