Translocations involving ETS family proteins in human cancer.

Elizabeth A Fry,Ali Mallakin,Kazushi Inoue

doi:10.15761/icst.1000281

Elizabeth A Fry, Ali Mallakin + Show 1 more

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https://doi.org/10.15761/icst.1000281

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Abstract

The ETS transcription factors regulate expression of genes involved in normal cell development, proliferation, differentiation, angiogenesis, and apoptosis, consisting of 28 family members in humans. Dysregulation of these transcription factors facilitates cell proliferation in cancers, and several members participate in invasion and metastasis by activating certain gene transcriptions. ETS1 and ETS2 are the founding members of the ETS family and regulate transcription by binding to ETS sequences. Three chimeric genes involving ETS genes have been identified in human cancers, which are EWS-FLI1 in Ewing's sarcoma, TMPRSS2-ERG in prostate cancer, and ETV6-RUNX1 in acute lymphocytic leukemia. Although these fusion transcripts definitely contribute to the pathogenesis of the disease, the impact of these fusion transcripts on patients' prognosis is highly controversial. In the present review, the roles of ETS protein translocations in human carcinogenesis are discussed.

Highlights

The oncogene v-Ets was discovered as a component of a chimeric gene, along with a truncated v-Myb gene, present in the genome of E26, an avian leukosis virus [1,2,3]
The human ETS factors are classified into 11 subgroups: ETS (ETS1/2), ERG, FLI1, ETV (PEA3, ETV1/4/5), TEL (ETV6/7), ELG (GABPα), ternary complex factor (TCF) (ELK1/3/4), ELF (ELF1/2/4), SPI1 (SPI1/B/C), ERF (ERF, ETV3, ETV3L), and FEV (Figure 1) [4]
A subset of four ETS family genes (ELF3, ELF5, EHF, SPDEF) has been placenta-specific subgroup based upon their restricted expression to tissues with high epithelial cell content (4-6); there are total of 28 ETS proteins in humans [4,5]

Summary

Introduction

The oncogene v-Ets was discovered as a component of a chimeric gene, along with a truncated v-Myb gene, present in the genome of E26, an avian leukosis virus [1,2,3]. It has been reported that the TMPRSS-ERG translocation is found in 50% of prostate cancer (PCa), and is associated with prognosis (Figure 1B) [17,18,19]. TMPRSS2-ERG fusion gene in prostate cancer (PCa)

Results

Conclusion