scholarly journals SUN-735 Functional Analysis of Testis-Specific Noncoding Genes in Estrogen-Dependent Transcription

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Ramesh Choudhari ◽  
Barbara Yang ◽  
Enrique Ivan Ramos ◽  
Mina Zilaie ◽  
Laura A Sanchez-Michael ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Genomic Analysis ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Mcf 7

Abstract Emerging studies have shown that germ cell (GC)-specific genes play critical roles in several cancers. The expression of these genes is tightly regulated and restricted to testis; however, many of them escape regulation and become aberrantly expressed in tumors. Interestingly, our genomic analysis suggests that several of these genes are long noncoding RNAs (lncRNAs) and are located at regions previously considered to be gene deserts in the human genome. In this regard, we used an integrated genomic approach to identify GC-lncRNA genes that are overexpressed in breast cancer. Further, by incorporating gene expression analysis from RNA-seq data from MCF-7 and T47D breast cancer cells, we generated a comprehensive list of estrogen-regulated GC-lncRNA genes. We hypothesize that GC-lncRNA genes regulate estrogen-dependent signaling in breast cancer. The selected genes: (a) CAERRC (Chromatin Associated Estrogen-Regulated RNA in Cancer, (b) LncRNA568, (c) LncRNA16 are primate-specific, and exclusively expressed in testis. All of them are regulated by estrogen, and their expression predicts poor outcome in ERα+ breast cancer patients. They have now been fully annotated (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure), and cloned. Further, we have created gene-specific KO MCF-7 cell lines using CRISPR to study their molecular roles. Our data suggest that these genes regulate estrogen-dependent gene expression and tumor growth in breast cancer cells. Genome-wide analysis of ERα binding and gene expression data indicate that they play a critical role in the estrogen-dependent transcription. Collectively, our results suggest that GC-genes, including CAERRC, LncRNA568, and LncRNA16, are excellent targets with prognostic and therapeutic potential in ER+ breast cancers.

C/EBPδ Modulates Cell Growth, Differentiation and Apoptosis of Myeloid Leukemia, Prostate and Breast Cancer Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4300-4300
Author(s):  
Sigal Gery ◽  
Sakae Stanosaki ◽  
Takayuki Ikezoe ◽  
Wolf K. Hofmann ◽  
Adrian F. Gombart ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Myeloid Leukemia ◽  
Breast Cancer Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Critical Role ◽  
Leukemic Cells ◽  
Granulocytic Differentiation ◽  
Mcf 7

Abstract C/EBPδ belongs to the family of highly conserved CCAAT/enhancer binding protein (C/EBP) transcription factors. Members of this family play a critical role in the regulation of mitotic growth arrest and differentiation in numerous cell types. To examine the consequences of C/EPBδ expression, we transfected C/EPBδ into CML myeloid leukemia (KCL22, K562), prostate (LNCaP, PC3, DU145), and breast (MCF-7, T47D, MDA-MB-231) cancer cell lines. C/EBPδ expression resulted in a proliferative arrest and an increase in apoptosis of the myeloid leukemia cells, as well as the prostate cells LNCaP and PC3, and the breast cells MCF-7 and T47D. In contrast, DU145 prostate and MDA-MB-231 breast cancer cells were not inhibited by C/EBPδ, indicating that the biologically properties of C/EBPδ depend upon its cellular context. We further studied the molecular mechanisms underlying the affect of C/EPBδ expression in CML leukemic cells. Myeloid differentiation of KCL22 and K562 blast cells as shown by morphologic changes and induction of secondary specific granule genes, occurred within 4 days of inducing expression of C/EBPδ. Furthermore, expression of C/EBPδ was associated with downregulation of c-Myc and cyclin E, and upregulation of the forkhead transcription factor FoxO1a (FKHR) and the cyclin-dependent kinase inhibitor p27Kip1. In addition, microarray analysis showed that C/EBPδ mRNA is upregulated during granulocytic differentiation of normal CD34+ bone marrow cells, suggesting that C/EBPδ is involved in lineage-specific differentiation. Taken together, these results show that expression of C/EBPδ in BCR-ABL-positive CML cells in blast crisis, is sufficient for neutrophil differentiation and suggest that ectopic induction of C/EBPδ in the blastic phase of CML, as well as in certain cases of prostate and breast cancers, may hold promising therapeutic potential.

The Expression of Dopamine Receptors Gene and their Potential Role in Targeting Breast Cancer Cells with Selective Agonist and Antagonist Drugs. Could it be the Novel Insight to Therapy?

2019 ◽  
Vol 16 (2) ◽  
pp. 184-197 ◽  
Author(s):  
Hossein Bakhtou ◽  
Asiie Olfatbakhsh ◽  
Abdolkhaegh Deezagi ◽  
Ghasem Ahangari
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Dopamine Receptors ◽  
Breast Cancer Cells ◽  
D2 Receptors ◽  
Healthy Individuals ◽  
Agonist And Antagonist ◽  
The Mean ◽  
Mcf 7

Background:Breast cancer is one of the common causes of mortality for women in Iran and other parts of the world. The substantial increasing rate of breast cancer in both developed and developing countries warns the scientists to provide more preventive steps and therapeutic measures. This study is conducted to investigate the impact of neurotransmitters (e.g., Dopamine) through their receptors and the importance of cancers via damaging immune system. It also evaluates dopamine receptors gene expression in the women with breast cancer at stages II or III and dopamine receptor D2 (DRD2) related agonist and antagonist drug effects on human breast cancer cells, including MCF-7 and SKBR-3.Methods:The patients were categorized into two groups: 30 native patients who were diagnosed with breast cancer at stages II and III, with the mean age of 44.6 years and they were reported to have the experience of a chronic stress or unpleasant life event. The second group included 30 individuals with the mean age of 39 years as the control group. In order to determine the RNA concentration in all samples, the RNA samples were extracted and cDNA was synthesized. The MCF-7 cells and SKBR-3 cells were treated with dopamine receptors agonists and antagonists. The MTT test was conducted to identify oxidative and reductive enzymes and to specify appropriate dosage at four concentrations of dopamine and Cabergoline on MCF-7 and SKBR-3 cells. Immunofluorescence staining was done by the use of a mixed dye containing acridine orange and ethidiume bromide on account of differentiating between apoptotic and necrotic cells. Flow cytometry assay was an applied method to differentiate necrotic from apoptotic cells.Results:Sixty seven and thirty three percent of the patients were related to stages II and III, respectively. About sixty three percent of the patients expressed ER, while fifty seven percent expressed PR. Thirty seven percent of the patients were identified as HER-2 positive. All types of D2-receptors were expressed in PBMC of patients with breast cancer and healthy individuals. The expression of the whole dopamine receptor subtypes (DRD2-DRD4) was carried out on MCF-7 cell line. The results of RT-PCR confirmed the expression of DRD2 on SKBR-3 cells, whereas the other types of D2- receptors did not have an expression. The remarkable differences in gene expression rates between patients and healthy individuals were revealed in the result of the Real-time PCR analysis. The over expression in DRD2 and DRD4 genes of PBMCs was observed in the patients with breast cancer at stages II and III. The great amount of apoptosis and necrosis occurred after the treatment of MCF-7 cells by Cabergoline from 25 to 100 µmolL-1 concentrations.Conclusion:This study revealed the features of dopamine receptors associated with apoptosis induction in breast cancer cells. Moreover, the use of D2-agonist based on dopamine receptors expression in various breast tumoral cells could be promising as a new insight of complementary therapy in breast cancer.

scholarly journals Transcriptional coregualtor NUPR1 maintains tamoxifen resistance in breast cancer cells

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Lingling Wang ◽  
Jiashen Sun ◽  
Yueyuan Yin ◽  
Yanan Sun ◽  
Jinyi Ma ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Critical Role ◽  
Endocrine Resistance ◽  
Autophagic Flux ◽  
Physical Interaction ◽  
Premature Senescence ◽  
Breast Cancers ◽  
Transcriptional Coregulator

AbstractTo support cellular homeostasis and mitigate chemotherapeutic stress, cancer cells must gain a series of adaptive intracellular processes. Here we identify that NUPR1, a tamoxifen (Tam)-induced transcriptional coregulator, is necessary for the maintenance of Tam resistance through physical interaction with ESR1 in breast cancers. Mechanistically, NUPR1 binds to the promoter regions of several genes involved in autophagy process and drug resistance such as BECN1, GREB1, RAB31, PGR, CYP1B1, and regulates their transcription. In Tam-resistant ESR1 breast cancer cells, NUPR1 depletion results in premature senescence in vitro and tumor suppression in vivo. Moreover, enforced-autophagic flux augments cytoplasmic vacuolization in NUPR1-depleted Tam resistant cells, which facilitates the transition from autophagic survival to premature senescence. Collectively, these findings suggest a critical role for NUPR1 as a transcriptional coregulator in enabling endocrine persistence of breast cancers, thus providing a vulnerable diagnostic and/or therapeutic target for endocrine resistance.

scholarly journals An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells

2011 ◽  
Vol 10 (1) ◽  
pp. 135 ◽  
Author(s):  
Yusuke Yamamoto ◽  
Yusuke Yoshioka ◽  
Kaho Minoura ◽  
Ryou-u Takahashi ◽  
Fumitaka Takeshita ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Genomic Analysis ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals ERβ-induced MFN2 inhibits the migration and invasiveness of breast cancer cells by inhibiting the P-AKT signaling pathway

2020 ◽  
Author(s):  
Mengyu Wei ◽  
Jun Hao ◽  
Xiaomei Liao ◽  
Yinfeng Liu ◽  
Ruihuan Fu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cells ◽  
Akt Pathway ◽  
Cancer Cell Migration ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Abstract Background Mitofusin 2 (MFN2) is localized on the outer membrane of mitochondria and is closely related to the migration of malignant tumor cells. Estrogen receptor β (ERβ) plays an anticancer role in breast cancer. Our previous experiments showed that ERβ can induce MFN2 expression, which then inhibits breast cancer cell migration. However, the exact mechanism by which ERβ-induced MFN2 inhibits breast cancer cell migration is unknown. Methods In this study, immunohistochemistry was first used to detect the expression of MFN2 in breast cancer tissues, and its relationship with the clinicopathological characteristics and prognosis of breast cancer patients was analyzed. MCF-7 and MDA-MB-231 cells were transfected with ERβ and MFN2 knockdown or expression plasmids. Western blot was used to detect the effects of ERβ on MFN2 and MFN2 on P-AKT473 and MMP2; the P-AKT pathway inhibitor LY294002 was administered to cells transfected with MFN2 knockdown plasmids, Western blot, immunocytofluorescence, and a wound healing assay revealed the effect of MFN2 on its downstream signaling pathway and the migration of breast cancer cells. Results This study found that the expression of MFN2 is related to the molecular type and prognosis of breast cancer patients ( P <0.05). The positive expression rate of MFN2 in triple-negative breast cancer was significantly lower than that in the HER2 + and luminal types. However, MFN2 expression was unrelated to age, tumor size, lymph node metastasis, TNM stage, histological type and grade ( P >0.05); ERβ positively regulated MFN2 expression and reduced the migration of both MCF-7 and MDA-MB-231 cells, while MFN2 knockdown increased the expression of P-AKT473 and MMP2. In contrast, the overexpression of MFN2 inhibited the expression of P-AKT473 and MMP2. These results showed that in MFN2 knockdown cells treated with LY294002, P-AKT473 and MMP2 expression levels were reversed. The reversal of P-AKT473 and MMP2 expression levels inhibits the invasiveness of human breast cancer cells. Conclusion MFN2 is related to the molecular subtype and prognosis of breast cancer. In human breast cancer MCF-7 and MDA-MB-231 cells, ERβ-induced MFN2 can inhibit the P-AKT pathway, which inhibits the invasiveness and migration of both breast cancer cell lines.

scholarly journals Mummy Induces Apoptosis Through Inhibiting of Epithelial-Mesenchymal Transition (EMT) in Human Breast Cancer Cells

2020 ◽  
Vol 9 ◽  
pp. 1812
Author(s):  
Solmaz Rahmani Barouji ◽  
Arman Shahabi ◽  
Mohammadali Torbati ◽  
Seyyed Mohammad Bagher Fazljou ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Control Group ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Mcf 7

Background: Mummy (Iranian pure shilajit) is a remedy with possessing anti-inflammatory, antioxidant and anticancer activities. This study aimed to examine mummy effects on epithelial-mesenchymal transition (EMT) and invasiveness of MCF-7 and MDA-MB-231 breast cancer (BC) cell lines with underlying its mechanism. Materials and Methods: The dose-dependent inhibitory effect of the mummy on cell proliferation in vitro was determined using the MTT assay.  Flow cytometry and 4’,6-diamidino-2-phenylindole dihydrochloride staining were respectively used for quantitative and qualitative analysis of cellular apoptosis, and gene expression analysis was conducted using real-time PCR. Results: MDA-MB-231 showed more sensitivity than the MCF-7 cell line to the anticancer activity of mummy, while mummy did not exhibit significant cell cytotoxicity against human normal cells (MCF-10A). The gene expression profile demonstrated a significant decrease in TGF-β1, TGF-βR1, TWIST1, NOTCH1, CTNNB1, SRC along with an increase in E-cadherin mRNA levels in mummy treated cells compared to the untreated control group (P≤0.05). Conclusion: Mummy triggers inhibition of EMT and metastasis in breast cancer cells mainly through the downregulation of TGFβ1 activity, and more studies required to find its specific anticancer activity with details. [GMJ.2020;9:e1812]

scholarly journals Melatonin enhances the apoptotic effects and modulates the changes in gene expression induced by docetaxel in MCF‑7 human breast cancer cells

2017 ◽  
Author(s):  
Carolina Alonso-Gonz�lez ◽  
Javier Men�ndez-Men�ndez ◽  
Alicia Gonz�lez-Gonz�lez ◽  
Alicia Gonz�lez ◽  
Samuel Cos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Apoptotic Effects ◽  
Mcf 7
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