The Ets family member Erg gene is expressed in mesodermal tissues and neural crests at fundamental steps during mouse embryogenesis

Vlaeminck-Guillem, Virginie; Carrère, Séverine; Dewitte, Frédérique; Stéhelin, D; Desbiens, Xavier; Duterque-Coquillaud, Martine

doi:10.1016/s0925-4773(99)00272-5

Cited by 79 publications

(75 citation statements)

References 9 publications

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“…(42)]. In this study, we showed that ERG, a transcription factor associated with precartilaginous condensation and chondrogenesis preceding bone formation (43,44), binds to the OPN promoter and transactivates this gene. Through EMSA experiments, a functional and conserved cis-regulated enhancer site was localized at nt À118 to À115.…”

Section: Discussionmentioning

confidence: 85%

Abnormal Expression of the ERG Transcription Factor in Prostate Cancer Cells Activates Osteopontin

Flajollet

Tian

Flourens

et al. 2011

Molecular Cancer Research

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Osteopontin (OPN) is an extracellular matrix glycophosphoprotein that plays a key role in the metastasis of a wide variety of cancers. The high level of OPN expression in prostate cells is associated with malignancy and reduced survival of the patient. Recent studies on prostate cancer (PCa) tissue have revealed recurrent genomic rearrangements involving the fusion of the 5 0 untranslated region of a prostate-specific androgen-responsive gene with a gene coding for transcription factors from the ETS family. The most frequently identified fusion gene is TMPRSS2:ERG, which causes ERG protein overexpression in PCa cells. ERG is a transcription factor linked to skeletogenesis. This study was designed to test whether ERG and the product of the TMPRSS2:ERG fusion gene modulate OPN gene expression in PCa cells. To characterize ERG and TMPRSS2:ERG transcriptional activity of OPN, we focused on ETS binding sites (EBS) localized in conserved regions of the promoter. Using in vitro and in vivo molecular assays, we showed that ERG increases OPN expression and binds to an EBS (nt À115 to À118) in the OPN promoter. Moreover, stable transfection of prostate tumor cell lines by TMPRSS2:ERG upregulates endogenous OPN expression. Finally, in human prostate tumor samples, detection of the TMPRSS2:ERG fusion gene was significantly associated with OPN overexpression. Taken together, these data suggest that OPN is an ERG-target gene in PCa where the abnormal expression of the transcription factor ERG, due to the TMPRSS2: ERG fusion, disturbs the expression of genes that play an important role in PCa cells and associated metastases. Mol Cancer Res; 9(7); 914-24. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 85%

Abnormal Expression of the ERG Transcription Factor in Prostate Cancer Cells Activates Osteopontin

Flajollet

Tian

Flourens

et al. 2011

Molecular Cancer Research

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“…It has been characterized as the earliest marker of blood vessels during embryogenesis 14 and has been shown to be expressed in endothelial and mesodermal tissues. 15 Its usefulness as a vascular marker has been demonstrated. 16 Nuclear FLI-1 expression has not been found in normal tissues other than endothelial cells and lymphocytes, but has been detected in Merkel cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Solid pseudopapillary neoplasms of the pancreas are associated with FLI-1 expression, but not with EWS/FLI-1 translocation

et al. 2006

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Solid pseudopapillary neoplasms of the pancreas are rare pancreatic tumors with mostly benign behavior, affecting almost exclusively women. Their histogenetic origin is still unsolved, but a recently reported EWS/FLI-1 translocation t(11;22)(q24;q21) and the consistent expression of CD56 and the progesterone receptor, both genes located on the long arm of chromosome 11, point to chromosome 11q as a potential locus of gene aberration in solid pseudopapillary neoplasms. To further elucidate this issue, we studied 30 cases of solid pseudopapillary neoplasms by comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH) and immunohistochemistry. Immunohistochemically, 38% showed nuclear expression of FLI-1 and all cases revealed positivity for CD56 and the progesterone receptor, whereas no solid pseudopapillary neoplasm expressed CD34. No translocation of the EWS gene was found by FISH and no gross chromosomal gain or loss was detected by CGH. It is concluded that FLI-1 expression in solid pseudopapillary neoplasms is not associated with an EWS/FLI-1 translocation. In addition, there are no chromosomal gains or losses, especially on chromosome 11, where the FLI-1 gene is located adjacent to the gene for CD56 (NCAM). These data add another feature to the complex phenotypic appearance of solid pseudopapillary neoplasms. (Figure 1) and show a striking female preponderance. 1 Ninety to 95% of these unusual pancreatic neoplasms behave benignly, whereas others are malignant, developing metastases in the mesenterium and the liver. So far, no specific marker for predicting the course of the disease exists, unless the tumor shows clear histological signs of malignancy. 2 Although a number of studies have been performed, it is still unknown what the direction of differentiation is for the pancreatic solid pseudopapillary neoplasm. Nor do we have much knowledge about genetic changes in solid pseudopapillary neoplasms. At the molecular level, it was recently shown that solid pseudopapillary neoplasms harbor a mutation in exon 3 of the b-catenin gene, which is associated with aberrant nuclear expression of b-catenin. 3,4 Other genetic aberrations of solid pseudopapillary neoplasms include an EWS/FLI-1 translocation t(11;22)(q24;q12), 5 a translocation t(13;17)(q14;p11), 6 derivatives of chromosomes 1, 14, and 20 7 and trisomy 3. 8 A solid pseudopapillary neoplasm investigated by comparative genomic hybridization (CGH) did not show any gross aberrations. 9 To elucidate the role of a probable EWS/FLI-1 translocation and the involvement of chromosome 11, we studied 30 well-characterized cases by CGH, fluorescent in situ hybridization (FISH) and with an additional panel of antibodies in order to screen this tumor entity for gross genetic aberrations. With this, we hoped to gain more information about the origin of solid pseudopapillary neoplasms and identify putative predictors of their clinical course. Materials and methodsThe study was performed on tumor resection specimens from 30 patients with solid pseudo...

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“…The only extramesodermal expression of Erg occurs at E8.5 in migrating neural cells. This expression ceases with settlement and formation of dorsal root ganglia (Vlaeminck-Guillem et al, 2000).…”

Section: An Overview Of the Expression Patterns Of Ets Family Membersmentioning

confidence: 99%

“…During embryogenesis, Erg is also highly expressed throughout the formation of the vascular tree, including both intraand extra-embryonic endothelia (Table 1). Subsequently, endothelial expression decreases until Erg expression is restricted to the forming capillaries of the embryo (Vlaeminck-Guillem et al, 2000). Mesodermal expression of Erg initiates in the branchial arches and extends to the anterior limb bud.…”

Section: An Overview Of the Expression Patterns Of Ets Family Membersmentioning

confidence: 99%

“…Mouse Fli1 was ®rst identi®ed as a site of Friend virus integration (Ben-David et al, 1991) and human Fli1 was originally cloned from a T cell leukemia line (Watson et al, 1992). The embryonic expression pattern of Fli1 is parallel to that of Erg in both endothelial and mesodermal tissues, including the urogenital tract and precartilaginous regions (Table 1) (Vlaeminck-Guillem et al, 2000). It is preferentially expressed in hematopoietic lineages and endothelial cells (Melet et al, 1996).…”

Section: An Overview Of the Expression Patterns Of Ets Family Membersmentioning

confidence: 99%

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Expression and function of Ets transcription factors in mammalian development: a regulatory network

2000

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The Ets family member Erg gene is expressed in mesodermal tissues and neural crests at fundamental steps during mouse embryogenesis

Cited by 79 publications

References 9 publications

Abnormal Expression of the ERG Transcription Factor in Prostate Cancer Cells Activates Osteopontin

Abnormal Expression of the ERG Transcription Factor in Prostate Cancer Cells Activates Osteopontin

Solid pseudopapillary neoplasms of the pancreas are associated with FLI-1 expression, but not with EWS/FLI-1 translocation

Expression and function of Ets transcription factors in mammalian development: a regulatory network

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