scholarly journals Role of c-Myb during Prolactin-Induced Signal Transducer and Activator of Transcription 5a Signaling in Breast Cancer Cells

Endocrinology ◽  
2008 ◽  
Vol 150 (4) ◽  
pp. 1597-1606 ◽  
Author(s):  
Feng Fang ◽  
Michael A. Rycyzyn ◽  
Charles V. Clevenger
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Prolactin Receptor ◽  
Ectopic Expression ◽  
Cellular Level ◽  
Janus Kinase ◽  
Signal Transducer ◽  
Signaling Complex

Implicated in the pathogenesis of breast cancer, prolactin (PRL) mediates its function in part through the prolactin receptor (PRLr)-associated Janus kinase 2 (Jak2)/signal transducer and activator of transcription 5 (Stat5) signaling complex. To delineate the mechanisms of Stat5a regulation in breast cancer, transcription factor-transcription factor (TF-TF) array analysis was employed to identify associated transcriptional regulators. These analyses revealed a PRL-inducible association of Stat5a with the transcription factor and protooncogene c-Myb. Confirmatory co-immunoprecipitation studies using lysates from both T47D and MCF7 breast cancer cells revealed a PRL-inducible association between these transcription factors. Ectopic expression of c-Myb enhanced the PRL-induced expression from both composite and synthetic Stat5a-responsive luciferase reporters. Chromatin immunoprecipitation assays also revealed a PRL-inducible association between c-Myb and endogenous Stat5a-responsive CISH promoter, which was associated with an enhanced expression of CISH gene product at the RNA and protein levels. Small interfering RNA-mediated c-Myb knockdown impaired the PRL-induced mRNA expression of five Stat5-responsive genes. DNA binding-defective mutants of c-Myb, incapable of activating expression from a c-Myb-responsive reporter, maintained their ability to enhance a Stat5a-responsive reporter. At a cellular level, ectopic expression of c-Myb resulted in an increase in T47D proliferation. Taken together, these results indicate that c-Myb potentiates Stat5a-driven gene expression, possibly functioning as a Stat5a coactivator, in human breast cancer.

scholarly journals Growth Hormone Signaling in Human T47D Breast Cancer Cells: Potential Role for a Growth Hormone Receptor-Prolactin Receptor Complex

2011 ◽  
Vol 25 (4) ◽  
pp. 597-610 ◽  
Author(s):  
Jie Xu ◽  
Yue Zhang ◽  
Philip A. Berry ◽  
Jing Jiang ◽  
Peter E. Lobie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Growth Hormone Receptor ◽  
Combined Treatment ◽  
Janus Kinase ◽  
Metabolic Effects ◽  
Signal Transducer ◽  
Gh Treatment

GH receptor (GHR) and prolactin (PRL) receptor (PRLR) are structurally similar cytokine receptor superfamily members that are highly conserved among species. GH has growth-promoting and metabolic effects in various tissues in vertebrates, including humans. PRL is essential for regulation of lactation in mammals. Recent studies indicate that breast tissue bears GHR and PRLR and that both GH and PRL may impact development or behavior of breast cancer cells. An important facet of human GH (hGH) and human PRL (hPRL) biology is that although hPRL interacts only with hPRLR, hGH binds well to both hGHR and hPRLR. Presently, we investigated potential signaling effects of both hormones in the estrogen receptor- and progesterone receptor-positive human T47D breast cancer cell line. We found that this cell type expresses ample GHR and PRLR and responds well to both hGH and hPRL, as evidenced by activation of the Janus kinase 2/signal transducer and activator of transcription 5 pathway. Immunoprecipitation studies revealed specific GHR-PRLR association in these cells that was acutely enhanced by GH treatment. Although GH caused formation of disulfide-linked and chemically cross-linked GHR dimers in T47D cells, GH preferentially induced tyrosine phosphorylation of PRLR rather than GHR. Notably, both a GHR-specific ligand antagonist (B2036) and a GHR-specific antagonist monoclonal antibody (anti-GHRext-mAb) failed to inhibit GH-induced signal transducer and activator of transcription 5 activation. In contrast, although the non-GHR-specific GH antagonist (G120R) and the PRL antagonist (G129R) individually only partially inhibited GH-induced activation, combined treatment with these two antagonists conferred greater inhibition than either alone. These data indicate that endogenous GHR and PRLR associate (possibly as a GHR-PRLR heterodimer) in human breast cancer cells and that GH signaling in these cells is largely mediated by the PRLR in the context of both PRLR-PRLR homodimers and GHR-PRLR heterodimers, broadening our understanding of how these related hormones and their related receptors may function in physiology and pathophysiology.

A transcriptional repressive role for epithelial-specific ETS factor ELF3 on oestrogen receptor alpha in breast cancer cells

2016 ◽  
Vol 473 (8) ◽  
pp. 1047-1061 ◽  
Author(s):  
Vijaya Narasihma Reddy Gajulapalli ◽  
Venkata Subramanyam Kumar Samanthapudi ◽  
Madhusudana Pulaganti ◽  
Saratchandra Singh Khumukcham ◽  
Vijaya Lakhsmi Malisetty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Dna Binding ◽  
Cancer Cells ◽  
Oestrogen Receptor ◽  
Breast Cancer Cells ◽  
Transcriptional Activity ◽  
Ectopic Expression ◽  
Binding Activity ◽  
Dna Binding Activity

Oestrogen receptor-α (ERα) is a ligand-dependent transcription factor that primarily mediates oestrogen (E2)-dependent gene transcription required for mammary gland development. Coregulators critically regulate ERα transcription functions by directly interacting with it. In the present study, we report that ELF3, an epithelial-specific ETS transcription factor, acts as a transcriptional repressor of ERα. Co-immunoprecipitation (Co-IP) analysis demonstrated that ELF3 strongly binds to ERα in the absence of E2, but ELF3 dissociation occurs upon E2 treatment in a dose- and time-dependent manner suggesting that E2 negatively influences such interaction. Domain mapping studies further revealed that the ETS (E-twenty six) domain of ELF3 interacts with the DNA binding domain of ERα. Accordingly, ELF3 inhibited ERα’s DNA binding activity by preventing receptor dimerization, partly explaining the mechanism by which ELF3 represses ERα transcriptional activity. Ectopic expression of ELF3 decreases ERα transcriptional activity as demonstrated by oestrogen response elements (ERE)-luciferase reporter assay or by endogenous ERα target genes. Conversely ELF3 knockdown increases ERα transcriptional activity. Consistent with these results, ELF3 ectopic expression decreases E2-dependent MCF7 cell proliferation whereas ELF3 knockdown increases it. We also found that E2 induces ELF3 expression in MCF7 cells suggesting a negative feedback regulation of ERα signalling in breast cancer cells. A small peptide sequence of ELF3 derived through functional interaction between ERα and ELF3 could inhibit DNA binding activity of ERα and breast cancer cell growth. These findings demonstrate that ELF3 is a novel transcriptional repressor of ERα in breast cancer cells. Peptide interaction studies further represent a novel therapeutic option in breast cancer therapy.

scholarly journals Integrin α3β1 Promotes Invasive and Metastatic Properties of Breast Cancer Cells through Induction of the Brn-2 Transcription Factor

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 480
Author(s):  
Rakshitha Pandulal Miskin ◽  
Janine S. A. Warren ◽  
Abibatou Ndoye ◽  
Lei Wu ◽  
John M. Lamar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Breast Cancer Cells ◽  
Gene Promoter ◽  
Akt Inhibitor ◽  
Integrin Α3β1

In the current study, we demonstrate that integrin α3β1 promotes invasive and metastatic traits of triple-negative breast cancer (TNBC) cells through induction of the transcription factor, Brain-2 (Brn-2). We show that RNAi-mediated suppression of α3β1 in MDA-MB-231 cells caused reduced expression of Brn-2 mRNA and protein and reduced activity of the BRN2 gene promoter. In addition, RNAi-targeting of Brn-2 in MDA-MB-231 cells decreased invasion in vitro and lung colonization in vivo, and exogenous Brn-2 expression partially restored invasion to cells in which α3β1 was suppressed. α3β1 promoted phosphorylation of Akt in MDA-MB-231 cells, and treatment of these cells with a pharmacological Akt inhibitor (MK-2206) reduced both Brn-2 expression and cell invasion, indicating that α3β1-Akt signaling contributes to Brn-2 induction. Analysis of RNAseq data from patients with invasive breast carcinoma revealed that high BRN2 expression correlates with poor survival. Moreover, high BRN2 expression positively correlates with high ITGA3 expression in basal-like breast cancer, which is consistent with our experimental findings that α3β1 induces Brn-2 in TNBC cells. Together, our study demonstrates a pro-invasive/pro-metastatic role for Brn-2 in breast cancer cells and identifies a role for integrin α3β1 in regulating Brn-2 expression, thereby revealing a novel mechanism of integrin-dependent breast cancer cell invasion.

scholarly journals Involvement of c-Myc in the proliferation of MCF-7 human breast cancer cells induced by bHLH transcription factor DEC2

2014 ◽  
Vol 35 (3) ◽  
pp. 815-820 ◽  
Author(s):  
YUNYAN WU ◽  
HIDENOBU SATO ◽  
TAKAHIRO SUZUKI ◽  
TADASHI YOSHIZAWA ◽  
SATOKO MOROHASHI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Bhlh Transcription Factor ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mcf 7

Role of Prolactin Receptor in Growth Hormone Signaling in Human Breast Cancer Cells.

2010 ◽  
pp. OR33-6-OR33-6
Author(s):  
Jie Xu ◽  
Jing Jiang ◽  
Peter E Lobie ◽  
Serge Y Fuchs ◽  
Stuart J Frank
Keyword(s):  
Breast Cancer ◽  
Growth Hormone ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Prolactin Receptor ◽  
Hormone Signaling ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Apigenin induces caspase-dependent apoptosis by inhibiting signal transducer and activator of transcription 3 signaling in HER2-overexpressing SKBR3 breast cancer cells

2015 ◽  
Vol 12 (2) ◽  
pp. 2977-2984 ◽  
Author(s):  
HYE-SOOK SEO ◽  
JIN MO KU ◽  
HAN-SEOK CHOI ◽  
JONG-KYU WOO ◽  
BO-HYOUNG JANG ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Signal Transducer ◽  
Transcription 3

scholarly journals Glucocorticoid receptor–IRS-1 axis controls EMT and the metastasis of breast cancers

2019 ◽  
Vol 11 (12) ◽  
pp. 1042-1055 ◽  
Author(s):  
Weiwei Shi ◽  
Dongmei Wang ◽  
Xinwang Yuan ◽  
Yi Liu ◽  
Xiaojie Guo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Cell Survival ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Biological Effects ◽  
Ectopic Expression ◽  
Metastatic Breast ◽  
Mesenchymal Transition ◽  
Expression Levels

Abstract Glucocorticoid receptor (GR) is involved in the transcriptional regulation of genes that are important for various biological functions, including tumor growth and metastatic progression. However, the cellular and biological effects of GR remain poorly understood. Here, we investigated the role of GR and its underlying mechanism in mediating breast cancer cell survival and metastasis. We observed that the GR levels were increased in drug-resistant breast cancer cells and in metastatic breast cancer samples. GR promoted tumor cell invasion and lung metastasis in vivo. The GR expression levels were negatively correlated with the survival rates of breast cancer patients. Both ectopic expression and knockdown of GR revealed that GR is a strong inducer of epithelial-to-mesenchymal transition (EMT), which is consistent with its effects on cell survival and metastasis. GR suppressed the expression of insulin receptor substrate 1 (IRS-1) by acting as an IRS-1 transcriptional repressor. In addition, GR has an opposite effect on the expression levels of IRS-2, indicating that GR is able to differentially regulate the IRS-1 and IRS-2 expression. The cellular and biological effects elicited by GR were consistent with the reduced levels of IRS-1 observed in cancer cells, and GR-mediated IRS-1 suppression activated the ERK2 MAP kinase pathway, which is required for GR-mediated EMT. Taken together, our results indicate that GR–IRS-1 signaling axis plays an essential role in regulating the survival, invasion, and metastasis of breast cancer cells.

Suppression of estrogen receptor-alpha transactivation by thyroid transcription factor-2 in breast cancer cells

2012 ◽  
Vol 421 (3) ◽  
pp. 532-537 ◽  
Author(s):  
Eunsook Park ◽  
Eun-Yeung Gong ◽  
Maria Grazia Romanelli ◽  
Keesook Lee
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Transcription Factor ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Estrogen Receptor Alpha ◽  
Receptor Alpha ◽  
Thyroid Transcription Factor
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