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BMC Molecular Biology

, 18:20

Transcriptional control of gene expression

Abstract

BackgroundNuclear factors of activated T-cells NFATs have been mainly characterized in the context of immune response regulation because, as transcription factors, they have the ability to induce gene transcription. NFAT proteins are found in several types of tumors, for instance, pancreatic carcinoma. The role of NFATs in carcinogenesis is regulating central genes in cell differentiation and cell growth. NFAT proteins are primarily located in cytoplasm and only transported to the cell nucleus after activation. Here, they interact with other transcription factors cooperating with NFAT proteins, thus influencing the selection and regulation of NFAT-controlled genes. To identify and characterize possible interaction partners of the transcription factor NFATc2 in pancreatic carcinoma cells PaTu 8988t.

MethodsNFATc2 expression and the mode of action of Ionomycin in the pancreatic tumor cell lines PaTu 8988t were shown with Western blotting and immunofluorescence tests. Potential partner proteins were verified by means of immunoprecipitation and binding partners, their physical interactions with DNA pull-down assays, siRNA technologies, and GST pull-down assays. Functional evidence was complemented by reporter–promoter analyses.

ResultsNFATc2 and Sp1 are co-localized in cell nuclei and physically interact at the NFAT target sequence termed NFAT-responsive promotor construct. Sp1 increases the functional activity of its binding partner NFATc2. This interaction is facilitated by Ionomycin in the early stimulation phase up to 60 min.

ConclusionsOncological therapy concepts are becoming more and more specific, aiming at the efficient modulation of specific signal and transcription pathways. The oncogenic transcription partner Sp1 is important for the transcriptional and functional activity of NFATc2 in pancreatic carcinoma. The binding partners interact in cells. Further studies are necessary to identify the underlying mechanisms and establish future therapeutic options for treating this aggressive type of tumor.

KeywordsNFATc2 Sp1 Pancreatic carcinoma Binding partner Cancer AbbreviationsAP-1activator protein-1

C-EBPCCAAT-enhancer protein

CK1casein kinase 1

COX-2cyclooxygenase-2

CREBcAMP response element binding protein

DAPI4′6-diamino-2-phenylindole

EGFRepidermal growth factor receptor

EGRearly growth response gene

FCSfetal calf serum

FOXP3forkhead protein 3

GATAGATA binding facctor

GSK 3gycogensynthase kinase 3

KLFkruppel-like transkriptionsfactor

MEF 2Amyocyte enhancer Factor 2A

NFATnuclear factors of activated T-cells

siRNAsmall interfering RNA

Sp1specificity protein 1

SV40 Simian virus 40

SOX10SRY-Box 10

TGF ßtransforming growth factor beta

VEGFvascular epithelial growth factor

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Autor: Manuela Malsy - Bernhard Graf - Katrin Almstedt

Fuente: https://link.springer.com/







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