Ets target genes: past, present and future

Sementchenko, Victor; Watson, Dennis K.

doi:10.1038/sj.onc.1204034

Cited by 336 publications

(283 citation statements)

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“…Ets factors act as positive or negative regulators of the expression of genes that are involved in various biological processes, including control of cellular proliferation, differentiation, hematopoiesis, apoptosis, tissue remodeling, angiogenesis, and transformation [Sementchenko and Watson, 2000;Watson and Seth, 2000;Watson et al, 2001;Dittmer, 2003;Oikawa and Yamada, 2003]. Our recent literature survey allowed identification of over 200 Ets target genes [Sementchenko and Watson, 2000], and the number of genes regulated via EBS is constantly increasing. This number of Ets target genes is between those previously estimated for p53 (200-300 target genes) and for the hormone receptor family (50-100 genes).…”

Section: The Ets Gene Familymentioning

confidence: 99%

“…Among the multiple Ets target genes that are important for cancer progression are those that function in control of cell proliferation (cyclins and cdks), adhesion [cadherins, integrins, cell adhesion molecules (CAMs)], motility/migration (hepatocyte growth factor receptor c-Met, vimentin), cell survival (Bcl-2), invasion (uPA & uPAR, PAI, MMPs, TIMPs, heparanase), extravasation (MMPs, integrins), micro-metastasis [osteopontin, parathyroid hormone-related peptide (PTHrP), chemokines/chemokine receptors (RANTES, MIP-3α), CD44], and establishment and maintenance of distant site metastasis and angiogenesis (integrin β3, VEGF, Flt-1/KDR, Tie2) [Sementchenko and Watson, 2000;Oikawa and Yamada, 2003]. …”

Section: Ets Involvement In Migration Emt and Cancer Metastasismentioning

confidence: 99%

“…There are 25 human and 26 murine Ets family members. Ets factors control specific genes that perform critical roles in diverse processes, including cell proliferation, apoptosis, differentiation, lymphoid cell development, angiogenesis, and invasiveness [Sementchenko and Watson, 2000]. To date, studies in the field have largely focused on individual Ets factors and have indeed yielded valuable, albeit fragmented, information.…”

Section: Introductionmentioning

confidence: 99%

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Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

258

202

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The Ets family consists of a large number of evolutionarily conserved transcription factors, many of which have been implicated in tumor progression. Extensive studies on this family of proteins have focused so far mainly on the biochemical properties and cellular functions of individual factors. Since most of the Ets factors can bind to the core consensus DNA sequence GGAA/T in vitro, it has been a challenge to differentiate redundant from specific functions of various Ets proteins in vivo. Recent findings, however, suggest that such apparent redundancy may in fact be a central component of a network of differentially regulated specific Ets factors, resulting in distinct biological and pathological consequences. The programmed "Ets conversion" appears to play a critical role during tumor progression, especially in control of cellular changes during epithelial-mesenchymal transition and metastasis. Coordination of multiple Ets gene functions also mediates interactions between tumor and stromal cells. As such, these new insights may provide a novel view of the Ets gene family as well as a focal point for studying the complex biological control involved in tumor progression. KeywordsEts; transcriptional regulation; ECM; cancer; invasion; metastasis; EMT; epithelium; stroma The Ets family of proteins consists of a large number of evolutionarily conserved transcription factors. There are 25 human and 26 murine Ets family members. Ets factors control specific genes that perform critical roles in diverse processes, including cell proliferation, apoptosis, differentiation, lymphoid cell development, angiogenesis, and invasiveness [Sementchenko and Watson, 2000]. To date, studies in the field have largely focused on individual Ets factors and have indeed yielded valuable, albeit fragmented, information. Recent findings, on the other hand, have suggested that several Ets factors may participate in a coordinated program that modulates cell migration and invasiveness, thus affecting tumor progression toward metastasis. In this review, we will examine the recent progress in Ets biology and provide a forum for discussion on a systemic view of Ets functions. Detailed descriptions of Ets proteins and their functions have been provided in several recent reviews [Watson and Seth, 2000;Watson et al., 2001;Dittmer, 2003;Oikawa and Yamada, 2003].Cancer results from a multi-step series of genetic changes that lead to essential alterations in cell physiology such as loss of growth controls and normal apoptotic response as well as sustained angiogenesis, invasion, and metastasis [Hanahan and Weinberg, 2000]. While it is known that most human tumors are derived from epithelial cells that have undergone multiple genetic alterations [Hanahan and Weinberg, 2000], it is also becoming clear that the alterations

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Section: The Ets Gene Familymentioning

confidence: 99%

Section: Ets Involvement In Migration Emt and Cancer Metastasismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

258

202

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“…These proteins are expressed mainly in hematopoietic cells [4,5], however some are also expressed in epithelial cells [6][7][8][9][10][11]. Ets factors are known to play roles in skeletal development, haematopoiesis, neural synapse formation, immunomodulation, metastasis, cellular proliferation and differentiation, and apoptosis [12][13][14]. Some members of this family have also been implicated in tumorigenesis [15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1

YANIW,

2005

Cell Res

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The role of Ese-2, an Ets family transcription factor, in gene regulation is not known. In this study, the interaction between Ese-2 and cytokeratin 18 (K18) intron 1 was characterized in lung epithelial cells. Reporter gene assays showed Ese-2 was able to upregulate K18 intron 1 enhanced reporter gene expression by approximately 2-fold. We found that full length Ese-2 did not bind DNA strongly, therefore truncated versions of the protein, containing the ETS domain or Pointed domain, were created and tested in electrophoresis mobility shift assays. Multiple interactions between the ETS domain and putative DNA binding sites within K18 intron 1 were observed, which led to the determination of a possible Ese-2 DNA binding consensus sequence. These experiments suggest that Ese-2 could play a role in the regulation of K18 expression in lung epithelial cells.

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“…However, in our study there was no significant difference in the enhancement of PLD2 gene expression between EWS/Fli-1 and Fli-1 transfectants as shown in Figure 1b. Sementchenko and Watson (2000) reviewed the targets of ETS protein including Fli-1, which may activate or suppress the transcription of GATA-1 in a cell-type-specific manner. Here, we have shown that PLD2 is a novel target of EWS/Fli-1 as well as of Fli-1 transcription factor and that one ETS binding site (À126 to À120 bp from the transcription initiation point) works as the principal promoter of PLD2 gene.…”

Section: Discussionmentioning

confidence: 99%

Ewing's sarcoma fusion protein, EWS/Fli-1 and Fli-1 protein induce PLD2 but not PLD1 gene expression by binding to an ETS domain of 5′ promoter

et al. 2006

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It was reported that short interfering RNA (siRNA) of EWS/Fli-1 downregulated phospholipase D (PLD)2 in Ewing's sarcoma (EWS) cell line, suggesting that PLD2 is the target of aberrant transcription factor, EWS/Fli-1. Here, we further investigated the regulation of PLD2 gene expression by EWS/Fli-1 and Fli-1 in another EWS cell line, and also in EWS/Fli-1-or Fli-1-transfected cell line. EWS/Fli-1-or Fli-1-overexpressed cells showed higher PLD2 but not PLD1 protein expression and enhanced cell proliferation as compared to mock transfectant. The treatment of these cells with 1-butanol or siRNA of PLD2 inhibited cell growth, suggesting the pivotal role of PLD in cell growth promotion. PLD2 but not PLD1 mRNA level was also increased in EWS/Fli-1 or Fli-1-transfectants. After determining the transcription initiation points, we cloned the 5 0 promoter of both PLD1 and PLD2 and analysed promoter activities. Results showed that EWS/ Fli-1 and Fli-1 increase PLD2 gene expression by binding to an erythroblast transformation-specific domain (À126 to À120 bp from the transcription initiation site) of PLD2 promoter, which is the minimal and most powerful region. Electrophoresis mobility shift assay using truncated proteins showed that both DNA-binding domain and trans-activating domain were necessary for the enhanced gene expression of PLD2.

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Ets target genes: past, present and future

Cited by 336 publications

References 333 publications

Ets proteins in biological control and cancer

Ets proteins in biological control and cancer

Epithelium-specific ets transcription factor 2 upregulates cytokeratin 18 expression in pulmonary epithelial cells through an interaction with cytokeratin 18 intron 1

Ewing's sarcoma fusion protein, EWS/Fli-1 and Fli-1 protein induce PLD2 but not PLD1 gene expression by binding to an ETS domain of 5′ promoter

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