TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation

C. Sun; A. Dobi; A. Mohamed; H. Li; R. L. Thangapazham; B. Furusato; S. Shaheduzzaman; S. H. Tan; G. Vaidyanathan; E. Whitman; D. J. Hawksworth; Y. Chen; M. Nau; V. Patel; M. Vahey; J. S. Gutkind; T. Sreenath; G. Petrovics; I. A. Sesterhenn; D. G. McLeod; S. Srivastava

doi:10.1038/onc.2008.183

TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation

C. Sun, A. Dobi^*, A. Mohamed, H. Li, R. L. Thangapazham, B. Furusato, S. Shaheduzzaman, S. H. Tan, G. Vaidyanathan, E. Whitman, D. J. Hawksworth, Y. Chen, M. Nau, V. Patel, M. Vahey, J. S. Gutkind, T. Sreenath, G. Petrovics, I. A. Sesterhenn, D. G. McLeodS. Srivastava

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

211 Scopus citations

Abstract

The high prevalence of TMPRSS2-ERG rearrangements (∼60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

Original language	English
Pages (from-to)	5348-5353
Number of pages	6
Journal	Oncogene
Volume	27
Issue number	40
DOIs	https://doi.org/10.1038/onc.2008.183
State	Published - 11 Sep 2008
Externally published	Yes

Keywords

C-MYC
ERG
Oncogene
PSA
Prostate cancer
TMPRSS2-ERG

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Sun, C., Dobi, A., Mohamed, A., Li, H., Thangapazham, R. L., Furusato, B., Shaheduzzaman, S., Tan, S. H., Vaidyanathan, G., Whitman, E., Hawksworth, D. J., Chen, Y., Nau, M., Patel, V., Vahey, M., Gutkind, J. S., Sreenath, T., Petrovics, G., Sesterhenn, I. A., ... Srivastava, S. (2008). TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation. Oncogene, 27(40), 5348-5353. https://doi.org/10.1038/onc.2008.183

@article{3c59fb9d99434fca85fb44e173d804b2,

title = "TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation",

abstract = "The high prevalence of TMPRSS2-ERG rearrangements (∼60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.",

keywords = "C-MYC, ERG, Oncogene, PSA, Prostate cancer, TMPRSS2-ERG",

author = "C. Sun and A. Dobi and A. Mohamed and H. Li and Thangapazham, {R. L.} and B. Furusato and S. Shaheduzzaman and Tan, {S. H.} and G. Vaidyanathan and E. Whitman and Hawksworth, {D. J.} and Y. Chen and M. Nau and V. Patel and M. Vahey and Gutkind, {J. S.} and T. Sreenath and G. Petrovics and Sesterhenn, {I. A.} and McLeod, {D. G.} and S. Srivastava",

year = "2008",

month = sep,

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doi = "10.1038/onc.2008.183",

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Sun, C, Dobi, A, Mohamed, A, Li, H, Thangapazham, RL, Furusato, B, Shaheduzzaman, S, Tan, SH, Vaidyanathan, G, Whitman, E, Hawksworth, DJ, Chen, Y, Nau, M, Patel, V, Vahey, M, Gutkind, JS, Sreenath, T, Petrovics, G, Sesterhenn, IA, McLeod, DG & Srivastava, S 2008, 'TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation', Oncogene, vol. 27, no. 40, pp. 5348-5353. https://doi.org/10.1038/onc.2008.183

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T1 - TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation

AU - Sun, C.

AU - Dobi, A.

AU - Mohamed, A.

AU - Li, H.

AU - Thangapazham, R. L.

AU - Furusato, B.

AU - Shaheduzzaman, S.

AU - Tan, S. H.

AU - Vaidyanathan, G.

AU - Whitman, E.

AU - Hawksworth, D. J.

AU - Chen, Y.

AU - Nau, M.

AU - Patel, V.

AU - Vahey, M.

AU - Gutkind, J. S.

AU - Sreenath, T.

AU - Petrovics, G.

AU - Sesterhenn, I. A.

AU - McLeod, D. G.

AU - Srivastava, S.

PY - 2008/9/11

Y1 - 2008/9/11

N2 - The high prevalence of TMPRSS2-ERG rearrangements (∼60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

AB - The high prevalence of TMPRSS2-ERG rearrangements (∼60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

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KW - ERG

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DO - 10.1038/onc.2008.183

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AN - SCOPUS:51649115957

SN - 0950-9232

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SP - 5348

EP - 5353

JO - Oncogene

JF - Oncogene

IS - 40

ER -

TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation

Abstract

Keywords

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