Antibodies to ETS Oncoproteins

Introduction

ETS proteins are transcription factors that activate or repress the expression of genes that are involved in various biological processes, including cellular proliferation, differentiation, development, transformation and apoptosis. Identification of target genes that are regulated by a specific transcription factor is one of the most critical areas in understanding the molecular mechanisms that control transcription. Furthermore, identification of target gene promoters for normal and oncogenic transcription factors provides insight into the regulation of genes that are involved in control of normal cell growth, and differentiation, as well as provide information critical to understanding cancer development.

The ETS1 proto-oncoprotein is a member of the ETS family of transcription factors that share a unique DNA binding domain, the ETS domain. The DNA binding activity of ETS1 is controlled by kinases and transcription factors. Some transcription factors, such as AML-1, regulate ETS1 by targeting its autoinhibitory module. Others, such as Pax-5, alter ETS1 DNA binding properties. ETS1 harbors two phosphorylation sites, threonine-38 and an array of serines within the exon VII domain. Phosphorylation of threonine-38 by ERK1/2 activates ETS1, whereas phosphorylation of the exon VII domain by CaMKII or MLCK inhibits ETS1 DNA binding activity. ETS1 is expressed by numerous cell types. In haemotopoietic cells, it contributes to the regulation of cellular differentiation. In a variety of other cells, including endothelial cells, vascular smooth muscle cells and epithelial cancer cells, ETS1 promotes invasive behavior. Regulation of MMP1, MMP3, MMP9 and uPA as well as of VEGF and VEGF receptor gene expression has been ascribed to ETS1. In tumors, ETS1 expression is indicative of poorer prognosis. Erythroblastosis virus oncogene homolog 2 (ETS2) is a pro-oncogene, which is located in human chromosomal region 21q22.3 and encodes a 56 kD protein that is phosphorylated by a Ca2+-dependent mitogenic signal process. ETS2 gene expresses in various tissues, including blood, breast and prostate.

ETS2 may be involved in the regulation of cellular proliferation and differentiation and may play a critical role in T-cell activation and cytokines production. It is similarly transposed as a consequence of nonrandom chromosomal translocations; especially, the t (8;21)(q22;q22) translocation is the most frequently noted breakpoint involving chromosome 21 for acute myelogenous leukemia. An acute nonlymphoblastic leukemia with a complex t (6;18;21) chromosomal translocation, has so far been associated with higher expression level of ETS2. It had been reported that ETS2 gene was associated with the growth and invasion of breast carcinoma cells and was required to maintain the transformed state for human prostate cancer cells.

Peptide Competition Experiment

Left panel: Lysates from Jurkat cells untreated (1) or treated with hydrogen peroxide (2-5) were resolved on a 10% polyacrylamide gel and transferred to PVDF.

Membranes were blocked with a 3% milk-TBST buffer for one hour at room temperature, then were incubated with the ETS1[pThr38] antibody BP7064 overnight at 4°C in a 1% milk-TBST buffer, following prior incubation with: no peptide (1, 2), the nonphosphopeptide corresponding to the immunogen (3), a generic phosphothreonine-containing peptide (4), or the phosphopeptide immunogen (5). After washing, membranes were incubated with goat F(ab’)2 anti-rabbit IgG HRP conjugate and bands were detected using the Pierce SuperSignal™ method. The data show that only the peptide corresponding to ETS1 [pThr38] blocks the signal, verifying the specificity of the antibody.

Right panel: Lysates from Jurkat cells untreated (1) or treated with hydrogen peroxide (2-5) that were either pretreated with the MEK inhibitor PD98059 (3), the JNK inhibitor SP600125 (4), or the p38 inhibitor SB202190 (5). Western blotting was performed as described above using the ETS1[pThr38] antibody or an antibody recognizing total ETS protein. The data illustrate regulation of this phosphorylation site by the ERK branch of the MAPK signaling cascade.

Antibody Panel to ETS1 / ETS2

Acris Antibodies offers a range of polyclonal antibodies to ETS1 and ETS2 which can be used for Immunological detection methods like Immunohistochemistry and / or Western blot

Antibody Panel to ETS1 / ETS2

ETS1/ETS2–antibody.

Literature

Seth A, Watson DK. ETS transcription factors and their emerging roles in human cancer. Eur J Cancer. 2005 Oct 5; (Epub ahead of print).

Dittmer J. The Biology of ETS1 Proto-Oncogene (Review). Molecular cancer 2003; 2:29

Li X, Lu JY, Zhao LQ, Wang XQ, Liu GL, Liu Z, Zhou CN, Wu M, Liu ZH. Overexpression of ETS2 in human esophageal squamous cell carcinoma. World J Gastroenterol 2003 Feb 15; 9(2):205-208.

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