Identification of a Novel DNA Binding Site and a Transcriptional Target for Activating Transcription Factor 5 in C6 Glioma and MCF-7 Breast Cancer Cells

Estrogen has been closely associated with the genesis and malignant progression of breast cancer. However, the molecular mechanism underlying the effects of estrogen is far from being completely clarified. We previously developed a custom-made cDNA microarray consisting of approximately 200 estrogen-responsive genes in breast cancer cells. Using this system, we found one estrogen-induced gene in various cancer cell lines, including breast cancer MCF-7 cells, which encode a zinc-finger transcription factor, EGR3 (early growth response 3). Northern blot analysis of estradiol-treated MCF-7 cells showed rapid and robust induction of Egr3, and addition of cycloheximide or ICI 182,780 suggested that Egr3 is the bona fide target for the estrogen receptor alpha (ERalpha). Using stable transformants derived from MCF-7 cells which were transfected with expression-controllable Egr3-expression vector, we demonstrated that Nab2 is one of the target genes for EGR3. Microarray analysis of the transformants revealed other candidate EGR3-induced genes. These strategies could be useful for analyzing downstream genes of ERalpha, and may contribute to elucidating the extensive signaling network of estrogen stimuli. Furthermore, a reporter assay using the upstream region of fasL probably involving escape from the immune system revealed that fasL is another target gene for EGR3. The roles of EGR3 in the physiology of breast cancer are discussed.

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Synthesis, biological evaluation, and molecular modelling of new naphthalene-chalcone derivatives as potential anticancer agents on MCF-7 breast cancer cells by targeting tubulin colchicine binding site

Journal of Enzyme Inhibition and Medicinal Chemistry ◽

10.1080/14756366.2019.1690479 ◽

2019 ◽

Vol 35 (1) ◽

pp. 139-144 ◽

Cited By ~ 14

Author(s):

Guangcheng Wang ◽

Wenjing Liu ◽

Zipeng Gong ◽

Yong Huang ◽

Yongjun Li ◽

...

Keyword(s):

Breast Cancer ◽

Binding Site ◽

Cancer Cells ◽

Anticancer Agents ◽

Molecular Modelling ◽

Breast Cancer Cells ◽

Biological Evaluation ◽

Chalcone Derivatives ◽

Colchicine Binding Site ◽

Mcf 7

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Sodium Channel Nav1.5 Controls Epithelial-to-Mesenchymal Transition and Invasiveness in Breast Cancer Cells Through its Regulation by the Salt-Inducible Kinase-1

Scientific Reports ◽

10.1038/s41598-019-55197-5 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 4

Author(s):

Frédéric Gradek ◽

Osbaldo Lopez-Charcas ◽

Stéphanie Chadet ◽

Lucile Poisson ◽

Lobna Ouldamer ◽

...

Keyword(s):

Breast Cancer ◽

Transcription Factor ◽

Cancer Cells ◽

Breast Cancer Cells ◽

Epithelial To Mesenchymal Transition ◽

Aberrant Expression ◽

Mesenchymal Transition ◽

Voltage Gated Sodium Channels ◽

Cell Invasiveness ◽

Mcf 7

AbstractLoss of epithelial polarity and gain in invasiveness by carcinoma cells are critical events in the aggressive progression of cancers and depend on phenotypic transition programs such as the epithelial-to-mesenchymal transition (EMT). Many studies have reported the aberrant expression of voltage-gated sodium channels (NaV) in carcinomas and specifically the NaV1.5 isoform, encoded by the SCN5A gene, in breast cancer. NaV1.5 activity, through an entry of sodium ions, in breast cancer cells is associated with increased invasiveness, but its participation to the EMT has to be clarified. In this study, we show that reducing the expression of NaV1.5 in highly aggressive human MDA-MB-231 breast cancer cells reverted the mesenchymal phenotype, reduced cancer cell invasiveness and the expression of the EMT-promoting transcription factor SNAI1. The heterologous expression of NaV1.5 in weakly invasive MCF-7 breast cancer cells induced their expression of both SNAI1 and ZEB1 and increased their invasive capacities. In MCF-7 cells the stimulation with the EMT-activator signal TGF-β1 increased the expression of SCN5A. Moreover, the reduction of the salt-inducible kinase 1 (SIK1) expression promoted NaV1.5-dependent invasiveness and expression of EMT-associated transcription factor SNAI1. Altogether, these results indicated a prominent role of SIK1 in regulating NaV1.5-dependent EMT and invasiveness.

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Novel mechanistic targets of Forkhead box Q1 transcription factor in human breast cancer cells

10.1101/2020.05.26.117176 ◽

2020 ◽

Author(s):

Su-Hyeong Kim ◽

Eun-Ryeong Hahm ◽

Krishna B. Singh ◽

Shivendra V. Singh

Keyword(s):

Breast Cancer ◽

Transcription Factor ◽

Cancer Cells ◽

Human Breast Cancer ◽

Breast Cancer Cells ◽

Rna Seq ◽

Human Breast ◽

Forkhead Box ◽

Luminal Type ◽

Mcf 7

The transcription factor forkhead box Q1 (FoxQ1), which is overexpressed in different solid tumors, has emerged as a key player in the pathogenesis of breast cancer by regulating epithelial-mesenchymal transition, maintenance of cancer-stem like cells, and metastasis. However, the mechanism underlying oncogenic function of FoxQ1 is still not fully understood. In this study, we compared the RNA-seq data from FoxQ1 overexpressing SUM159 cells with that of empty vector-transfected control (EV) cells to identify novel mechanistic targets of this transcription factor. Consistent with published results in basal-like subtype, immunohistochemistry revealed upregulation of FoxQ1 protein in luminal-type human breast cancer tissue microarrays when compared to normal mammary tissues. Many previously reported transcriptional targets of FoxQ1 (e.g., E-cadherin, N-cadherin, fibronectin 1, etc.) were verified from the RNA-Seq analysis. FoxQ1 overexpression resulted in downregulation of genes associated with cell cycle checkpoints, M phase, and cellular response to stress/external stimuli as evidenced from the Reactome pathway analysis. Consequently, FoxQ1 overexpression resulted in S, G2M and mitotic arrest in basal-like SUM159 and HMLE cells, but not in luminal-type MCF-7 cells. There were differences in expression of cell cycle-associated proteins between FoxQ1 overexpressing SUM159 and MCF-7 cells. Finally, we show for the first time that FoxQ1 is a direct transcriptional regulator of interleukin (IL)-1α, IL-8, and vascular endothelial growth factor in breast cancer cells. Chromatin immunoprecipitation revealed FoxQ1 occupancy at the promoters of IL-1α, IL-8, and VEGF. In conclusion, the present study reports novel mechanistic targets of FoxQ1 in human breast cancer cells.

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