ETS rearrangements and prostate cancer initiation - PubMed (original) (raw)

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. 2009 Feb 12;457(7231):E1; discussion E2-3.

doi: 10.1038/nature07738.

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ETS rearrangements and prostate cancer initiation

Brett S Carver et al. Nature. 2009.

Abstract

The first recurrent translocation event in prostate cancer has been recently described; it results in the translocation of an ETS (E26 transformation specific) transcription factor (ERG or ETV1) to the TMPRSS2 promoter region, which contains androgen responsive elements. The TMPRSS2:ERG genetic rearrangement has been reported to occur in approximately 40% of primary prostate tumours (ETV1 genetic rearrangements occur at a much lower frequency), and it results in the aberrant androgen-regulated expression of ERG. Tomlins et al. concluded that ETS genetic rearrangements are sufficient to initiate prostate neoplasia. However, here we show that ETS genetic rearrangements may in fact represent progression events rather than initiation events in prostate tumorigenesis. To this end, we demonstrate that the prostate-specific overexpression of ERG does not initiate prostate tumorigenesis.

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Figure 1

Figure 1. Prostate specific over-expression of ERG does not induce high grade prostatic intra-epithelial neoplasia

A total of 24 wild-type and 24 ERG transgenic mice were phenotypically characterized from one founding line after establishment that three independent founding lines produced a similar phenotype (A). Low (100X) and high (400X) power representative sections are shown for mice 6 months of age (ventral, anterior, and dorsal-lateral prostate lobes) demonstrating prominent nucleoli in wild-type mouse prostate glands. Representative histology of human high grade prostatic intra-epithelial neoplasia (HGPIN) and HGPIN in Pten heterozygous mice at 12 months of age (B). Immunohistochemical staining for Ki67 demonstrated no difference between wild-type mice and ERG transgenic mice (C).

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References

    1. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW, Varambally S, Cao X, Tchinda J, Kuefer R, Lee C, Montie JE, Shah RB, Pienta KJ, Rubin MA, Chinnaiyan AM. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science. 2005;310:644–8. - PubMed
    1. Tu JJ, Rohan S, Kao J, Kitabayashi N, Mathew S, Chen YT. Gene fusions between TMPRSS2 and ETS family genes in prostate cancer: frequency and transcript variant analysis by RT-PCR and FISH on paraffin-embedded tissues. Mod Pathol. 2007 [Epub ahead of print] - PubMed
    1. Perner S, Mosquera JM, Demichelis F, Hofer MD, Paris PL, Simko J, Collins C, Bismar TA, Chinnaiyan AM, De Marzo AM, Rubin MA. TMPRSS2-ERG fusion prostate cancer: an early molecular event associated with invasion. Am J Surg Pathol. 2007;31:882–8. - PubMed
    1. Tomlins SA, Bharathi L, Dhanasekaran SM, Helgeson BE, Cao X, Morris DS, Menon A, Jing A, Cao Q, Han B, Yu J, Wang L, Montie JE, Rubin MA, Pienta KJ, Roulston D, Shah RB, Varambally S, Mehra R, Chinnaiyan AM. Distinct classes of chromosomal rearrangements create oncogenic ETS gene fusions in prostate cancer. Nature. 2007;448:595–601. - PubMed

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