Mouse models in the study of the Ets family of transcription factors

Bartel, Frank; Higuchi, Tsukasa; Spyropoulos, Demetri D.

doi:10.1038/sj.onc.1204038

Cited by 100 publications

(77 citation statements)

References 42 publications

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“…To date, 13 of the 26 murine Ets genes (PU.1,SpiB,Ets1,Ets2,Tel,Fli1,PEA3,MEF,ER81,ERM,ESE1,ESE3,and SpiC) have been targeted by homologous recombination. These studies demonstrate important roles for Ets genes in embryogenesis and hematopoiesis [Bartel et al, 2000;Oikawa and Yamada, 2003]. …”

Section: Ets Target Genesmentioning

confidence: 91%

Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

255

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: Ets Target Genesmentioning

confidence: 91%

Ets proteins in biological control and cancer

Hsu

Trojanowska

Watson

2004

J of Cellular Biochemistry

255

202

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“…These findings are also unique when compared with previous studies utilizing knockout mouse models for other ETS genes in which no epithelial defects have been described. 50 Although a defect in terminal differentiation of the small intestinal epithelium during embryonic development has previously been demonstrated in Elf3À/À mice, 26 this is the first study to describe abnormal kinetics of cell proliferation and differentiation during repair of the injured bronchiolar epithelium in these mice. The cellular and molecular mechanisms of airway epithelial regeneration and repair are very complex and have been studied extensively in several laboratories; however, further studies are required in order to elucidate the exact role of Elf3 and other ETS transcription factors in this process.…”

Section: Discussionmentioning

confidence: 99%

Elf3 plays a role in regulating bronchiolar epithelial repair kinetics following Clara cell-specific injury

Oliver

Kushwah

et al. 2011

Laboratory Investigation

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“…ESE-1, ESE-2 and ESE-3 proteins, as well as some of the other Ets factors, also contain a pointed domain, which is involved in proteinprotein interactions [12]. Many Ets family members are expressed in hematopoietic cells [13]. However, the three ESE transcription factors are expressed only in organs that have specialized epithelial cells, such as intestine, kidney, prostate, pancreas and lung [8,9,[14][15][16][17][18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation

Duan

Cao

et al. 2008

Cell Res

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Airway inflammation is the hallmark of many respiratory disorders, such as asthma and cystic fibrosis. Changes in airway gene expression triggered by inflammation play a key role in the pathogenesis of these diseases. Genetic linkage studies suggest that ESE-2 and ESE-3, which encode epithelium-specific Ets-domain-containing transcription factors, are candidate asthma susceptibility genes. We report here that the expression of another member of the Ets family transcription factors ESE-1, as well as ESE-3, is upregulated by the inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in bronchial epithelial cell lines. Treatment of these cells with IL-1β and TNF-α resulted in a dramatic increase in mRNA expression for both ESE-1 and ESE-3. We demonstrate that the induced expression is mediated by activation of the transcription factor NF-κB. We have characterized the ESE-1 and ESE-3 promoters and have identified the NF-κB binding sequences that are required for the cytokine-induced expression. In addition, we also demonstrate that ESE-1 upregulates ESE-3 expression and downregulates its own induction by cytokines. Finally, we have shown that in Elf3 (homologous to human ESE-1) knockout mice, the expression of the inflammatory cytokine interleukin-6 (IL-6) is downregulated. Our findings suggest that ESE-1 and ESE-3 play an important role in airway inflammation.

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Mouse models in the study of the Ets family of transcription factors

Cited by 100 publications

References 42 publications

Ets proteins in biological control and cancer

Ets proteins in biological control and cancer

Elf3 plays a role in regulating bronchiolar epithelial repair kinetics following Clara cell-specific injury

Regulation of epithelium-specific Ets-like factors ESE-1 and ESE-3 in airway epithelial cells: potential roles in airway inflammation

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