Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51

Laitem, Clélia; Leprivier, Gabriel; Choul-Li, Souhaila; Bégué, Agnès; Monté, Didier; Larsimont, Denis; Dumont, Patrick; Duterque-Coquillaud, Martine; Aumercier, Marc

doi:10.1038/onc.2009.72

Cited by 43 publications

(59 citation statements)

References 45 publications

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“…These findings suggest that Ets-1 possesses a specificity of action for migration, but not invasion of PC3 prostate cancer cells. Furthermore, it suggests that the role of Ets-1 in migration of PC3 cells can not be fulfilled by other member of the ETS family which can replace each other under certain conditions (34).…”

Section: Discussionmentioning

confidence: 99%

Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells

Shaikhibrahim

Langer²,

Lindstrot³

et al. 2011

Oncol Rep

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Abstract. Different members of the Ets-family of transcription factors are involved in TMPRSS-2-Ets translocations frequently found in human prostate cancers. We previously reported that Ets-1, which is the prototype of Ets-family members, promotes both migration and invasion of melanoma, HeLa and glioma cells. Here, we examined whether Ets-1 has a similar effect upon migration and invasion of PC3 prostate cancer cells, and whether it is implicated in the regulation of the androgen co-regulator four and a half LIM only protein-2 (FHL2). Two stable PC3 cell cultures were established by transfection with either an Ets-1 inverse antisense expression vector or a mock control vector. Western blot analysis confirmed presence of Ets-1 in mock and absence in Ets-1 inverse cells. Microarray and qRT-PCR revealed an up-regulation of FHL2 in Ets-1 blocked cells, compared to mock. To examine the effects of Ets-1 upon cell migration, a wound assay was performed, and demonstrated that wounds were completely colonized by mock compared to Ets-1 blocked cells after 55 h. Evaluation of the effect upon invasion was examined using the Boyden chamber, which revealed no significant difference between mock and Ets-1 blocked cells. In conclusion, our study demonstrated for the first time that Ets-1 is implicated in the regulation of the androgen co-regulator FHL2, and reveals specificity of action for migration, but not invasion of PC3 prostate cancer cells.

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Section: Discussionmentioning

confidence: 99%

Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells

Shaikhibrahim

Langer²,

Lindstrot³

et al. 2011

Oncol Rep

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“…Interestingly, both inhibitory domains that surround the DNA-binding domain are conserved in ETS-1 p27, indicating that ETS-1 p27 is autoinhibited for DNA binding like the full length ETS-1 p51 (9).…”

Section: Introductionmentioning

confidence: 99%

“…The ETS-1 p51 protein and its splice variant p27 have been investigated in functional terms in mammary carcinoma cells (9). ETS-1 p27 has been shown to bind DNA in the same manner as ETS-1 p51 and to act both at a transcriptional and a subcellular level (9).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the ETS-1 p27 splice variant (without exons III-VI) lacks the threonine-38 residue, the pointed (PNT) and the transactivation (TAD) domains affecting the transcriptional activity of ETS-1 and the transactivation of its target genes (2,9). Interestingly, both inhibitory domains that surround the DNA-binding domain are conserved in ETS-1 p27, indicating that ETS-1 p27 is autoinhibited for DNA binding like the full length ETS-1 p51 (9).…”

Section: Introductionmentioning

confidence: 99%

“…The ETS-1 gene encodes three distinct proteins, ETS-1 p51 encoded by a full-length mRNA, ETS-1 p42 and ETS-1 p27 encoded by an alternatively spliced mRNA lacking exon VII and exons III-VI, respectively (8,9).…”

Section: Introductionmentioning

confidence: 99%

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Novel identification of the ETS-1 splice variants p42 and p27 in prostate cancer cell lines

et al. 2012

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Abstract. ETS-1 is involved in cellular functions such as proliferation, migration, invasion, apoptosis and angiogenesis. The ETS-1 gene encodes three distinct proteins, ETS-1 p51 encoded by a full-length mRNA, ETS-1 p42 and ETS-1 p27 encoded by an alternatively spliced mRNA lacking exon VII and exons III-VI, respectively. ETS-1 p51, commonly considered to be the active form, has been studied in prostate cancer (PCa). However, the ETS-1 p42 and p27 variants have not yet been identified in PCa. Therefore, we aimed in this study at investigating whether the splice variants p42 and p27 are expressed in the androgen-dependent VCaP and LNCaP and the androgen-independent PC3 and DU-145 PCa cell lines. Using RT-PCR, we found the expression of both splice variants p42 and p27 at the mRNA level in the VCaP, LNCaP, PC3 and DU-145 PCa cell lines. We then confirmed the expression of ETS-1 p51 and its splice variants p42 and p27 at the protein level using an anti-ETS-1 antibody directed against the DNA-binding domain (DBD) in lysates prepared from the latter-mentioned cell lines, as well as in PC3 cell nuclear extract. Moreover, differences in the expression ratios of the ETS-1 splice variants within each cell line were also found. In conclusion, we have demonstrated for the first time the novel identification of the ETS-1 splice variants p42 and p27 in PCa cell lines. It is very likely that the role of ETS-1 p51 in PCa is significantly influenced by the presence of its splice variants ETS-1 p42 and p27 as competi tion, abundance, affinity, interactions and cross-talk among them will eventually determine the genes that will be targeted and subsequently affect cellular functions. Follow-up studies will need to address in functional terms, the roles of these splice variants in PCa cell lines, as well as their expression in PCa tissues and its correlation with clinical outcome.

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Ets‐1 controls breast cancer cell balance between invasion and growth

Furlan

Vercamer

Bouali

et al. 2014

Intl Journal of Cancer

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Ets-1 overexpression in human breast cancers is associated with invasiveness and poor prognosis. By overexpressing Ets-1 or a dominant negative mutant in MMT breast cancer cells, we previously highlighted the key role of Ets-1 in coordinating multiple invasive features of these cells. Interestingly, we also noticed that Ets-1 decreased the density of breast cancer cells cultured in three-dimensional extracellular matrix gels. The 3D context was instrumental to this phenomenon, as such downregulation was not observed in cells grown on two-dimensional plastic or matrix-coated dishes. Ets-1 overexpression was deleterious to anchorage-independent growth of MMT cells in soft agar, a standard model for in vitro tumorigenicity. The relevance of this mechanism was confirmed in vivo, during primary tumor growth and in a metastatic assay of lung colonization. In these models, Ets-1 was associated with epithelial-to-mesenchymal transition features and modulated the ratio of Ki67-positive cells, while hardly affecting in vivo apoptotic cell death. Finally, siRNA-mediated knockdown of Ets-1 in human breast cancer cell lines also decreased colony growth, both in anchorage-independent assays and 3D extracellular matrix cultures. These in vitro and in vivo observations shed light on an unsuspected facet of Ets-1 in breast tumorigenesis. They show that while promoting malignancy through the acquisition of invasive features, Ets-1 also attenuates breast tumor cell growth and could therefore repress the growth of primary tumors and metastases. This work also demonstrates that 3D models may reveal mechanisms of tumor biology that are cryptic in standard 2D models.Breast cancer is the foremost cause of cancer-related deaths of women worldwide. The natural history of breast cancer classically involves progression from in situ hyperproliferative lesions to invasive carcinomas, eventually leading to metastatic disease. 1 The standard model of tumor progression relies on the sequential acquisition of genetic mutations conferring enhanced cell proliferation, survival, and invasiveness. Besides the high diversity among breast tumors, these malignancies are also characterized by great intratumoral heterogeneity. This is notably observed in terms of angiogenic, invasive and metastatic potential, and probably reflects a mixed population of cells at different stages of tumoral evolution. 2 Besides the genetic alterations driving tumor cell malignancy, cancer cells are also subjected to external stimuli from their microenvironment, which can foster their aggressiveness. In particular, epithelial-tomesenchymal transition (EMT) can be induced by tumorassociated reactive stroma, endowing carcinoma cells with the invasive properties required for intravasation. Elucidating the molecular mechanisms and master regulators of these transformative events is key to identifying new targets for anticancer therapy.The Ets-1 proto-oncogene is the prototype of the ETS family of transcription factors involved in the regulation of various biological functions. ...

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Ets-1 p27: a novel Ets-1 isoform with dominant-negative effects on the transcriptional properties and the subcellular localization of Ets-1 p51

Cited by 43 publications

References 45 publications

Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells

Ets-1 is implicated in the regulation of androgen co-regulator FHL2 and reveals specificity for migration, but not invasion, of PC3 prostate cancer cells

Novel identification of the ETS-1 splice variants p42 and p27 in prostate cancer cell lines

Ets‐1 controls breast cancer cell balance between invasion and growth

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