TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer

Todd Swanson, Sarah A. Krueger, Sandra Galoforo, Bryan J. Thibodeau, Alvaro A. Martinez, George D. Wilson, Brian Marples

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

PURPOSE/OBJECTIVES The androgen regulated transmembrane serine protease (TMPRSS2) and ETS transcription factor (ERG) gene fusion is a strong prognostic factor for disease recurrence following prostatectomy. Expression of TMPRSS2/ETS-related gene (ERG) fusion gene transcripts is linked with tumor proliferation, invasion, and an aggressive phenotype. The aim of this study was to define the effect of TMPRSS2/ERG fusion gene expression on chemo- and radiosensitivity in prostate tumor cell lines. MATERIALS/METHODS Clonogenic survival of PC3 and DU145 cells stably expressing TMPRSS2/ERG Types III and VI fusion genes was measured after X-irradiation (0-8Gy) and Paclitaxel. Cell cycle changes and DNA double-strand break induction and repair were assessed. Differential gene expression was measured by microarray analysis. ERG signaling pathway interactions were studied using Ariadne Pathway Studio. RESULTS Expression of the TMPRSS2/ERG fusions in PC3 cells increased radiation sensitivity and decreased paclitaxel sensitivity. Increased radiosensitivity was associated with persistent DNA breaks 24hr post-irradiation, down-regulation of genes involved in DNA repair and mitosis and up-regulation of ETV, an ETS transcription factor. However, DU145 Types III and VI demonstrated a different sensitivity phenotype and gene expression changes. Pathway analysis of ERG signaling further illustrated the variation between the PC3 and DU145 cell lines containing TMPRSS2/ERG fusions. CONCLUSIONS The effect of TMPRSS2/ERG gene fusions had differing effects on radiosensitivity and chemosensitivity depending on cell line and fusion type. Further work is needed with clinical samples to establish whether TMPRSS2/ERG gene fusions affect radio- and chemosensitivity in vivo.

Original languageEnglish (US)
Pages (from-to)1548-1558
Number of pages11
JournalProstate
Volume71
Issue number14
DOIs
StatePublished - Oct 1 2011

Fingerprint

Gene Fusion
Radio
Androgens
Prostatic Neoplasms
Cell Culture Techniques
Radiation Tolerance
Gene Expression
Genes
Paclitaxel
Transcription Factors
Phenotype
Cell Line
DNA Breaks
Double-Stranded DNA Breaks
Cell Fusion
Serine Proteases
Microarray Analysis
Prostatectomy
Tumor Cell Line
Mitosis

Keywords

  • cell lines
  • paclitaxel
  • prostate
  • radiosensitivity
  • TMPRSS2/ERG

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Swanson, T., Krueger, S. A., Galoforo, S., Thibodeau, B. J., Martinez, A. A., Wilson, G. D., & Marples, B. (2011). TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer. Prostate, 71(14), 1548-1558. https://doi.org/10.1002/pros.21371

TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer. / Swanson, Todd; Krueger, Sarah A.; Galoforo, Sandra; Thibodeau, Bryan J.; Martinez, Alvaro A.; Wilson, George D.; Marples, Brian.

In: Prostate, Vol. 71, No. 14, 01.10.2011, p. 1548-1558.

Research output: Contribution to journalArticle

Swanson, Todd ; Krueger, Sarah A. ; Galoforo, Sandra ; Thibodeau, Bryan J. ; Martinez, Alvaro A. ; Wilson, George D. ; Marples, Brian. / TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer. In: Prostate. 2011 ; Vol. 71, No. 14. pp. 1548-1558.
@article{45cff139765746519710dbe6263ec013,
title = "TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer",
abstract = "PURPOSE/OBJECTIVES The androgen regulated transmembrane serine protease (TMPRSS2) and ETS transcription factor (ERG) gene fusion is a strong prognostic factor for disease recurrence following prostatectomy. Expression of TMPRSS2/ETS-related gene (ERG) fusion gene transcripts is linked with tumor proliferation, invasion, and an aggressive phenotype. The aim of this study was to define the effect of TMPRSS2/ERG fusion gene expression on chemo- and radiosensitivity in prostate tumor cell lines. MATERIALS/METHODS Clonogenic survival of PC3 and DU145 cells stably expressing TMPRSS2/ERG Types III and VI fusion genes was measured after X-irradiation (0-8Gy) and Paclitaxel. Cell cycle changes and DNA double-strand break induction and repair were assessed. Differential gene expression was measured by microarray analysis. ERG signaling pathway interactions were studied using Ariadne Pathway Studio. RESULTS Expression of the TMPRSS2/ERG fusions in PC3 cells increased radiation sensitivity and decreased paclitaxel sensitivity. Increased radiosensitivity was associated with persistent DNA breaks 24hr post-irradiation, down-regulation of genes involved in DNA repair and mitosis and up-regulation of ETV, an ETS transcription factor. However, DU145 Types III and VI demonstrated a different sensitivity phenotype and gene expression changes. Pathway analysis of ERG signaling further illustrated the variation between the PC3 and DU145 cell lines containing TMPRSS2/ERG fusions. CONCLUSIONS The effect of TMPRSS2/ERG gene fusions had differing effects on radiosensitivity and chemosensitivity depending on cell line and fusion type. Further work is needed with clinical samples to establish whether TMPRSS2/ERG gene fusions affect radio- and chemosensitivity in vivo.",
keywords = "cell lines, paclitaxel, prostate, radiosensitivity, TMPRSS2/ERG",
author = "Todd Swanson and Krueger, {Sarah A.} and Sandra Galoforo and Thibodeau, {Bryan J.} and Martinez, {Alvaro A.} and Wilson, {George D.} and Brian Marples",
year = "2011",
month = "10",
day = "1",
doi = "10.1002/pros.21371",
language = "English (US)",
volume = "71",
pages = "1548--1558",
journal = "The Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "14",

}

TY - JOUR

T1 - TMPRSS2/ERG fusion gene expression alters chemo- and radio-responsiveness in cell culture models of androgen independent prostate cancer

AU - Swanson, Todd

AU - Krueger, Sarah A.

AU - Galoforo, Sandra

AU - Thibodeau, Bryan J.

AU - Martinez, Alvaro A.

AU - Wilson, George D.

AU - Marples, Brian

PY - 2011/10/1

Y1 - 2011/10/1

N2 - PURPOSE/OBJECTIVES The androgen regulated transmembrane serine protease (TMPRSS2) and ETS transcription factor (ERG) gene fusion is a strong prognostic factor for disease recurrence following prostatectomy. Expression of TMPRSS2/ETS-related gene (ERG) fusion gene transcripts is linked with tumor proliferation, invasion, and an aggressive phenotype. The aim of this study was to define the effect of TMPRSS2/ERG fusion gene expression on chemo- and radiosensitivity in prostate tumor cell lines. MATERIALS/METHODS Clonogenic survival of PC3 and DU145 cells stably expressing TMPRSS2/ERG Types III and VI fusion genes was measured after X-irradiation (0-8Gy) and Paclitaxel. Cell cycle changes and DNA double-strand break induction and repair were assessed. Differential gene expression was measured by microarray analysis. ERG signaling pathway interactions were studied using Ariadne Pathway Studio. RESULTS Expression of the TMPRSS2/ERG fusions in PC3 cells increased radiation sensitivity and decreased paclitaxel sensitivity. Increased radiosensitivity was associated with persistent DNA breaks 24hr post-irradiation, down-regulation of genes involved in DNA repair and mitosis and up-regulation of ETV, an ETS transcription factor. However, DU145 Types III and VI demonstrated a different sensitivity phenotype and gene expression changes. Pathway analysis of ERG signaling further illustrated the variation between the PC3 and DU145 cell lines containing TMPRSS2/ERG fusions. CONCLUSIONS The effect of TMPRSS2/ERG gene fusions had differing effects on radiosensitivity and chemosensitivity depending on cell line and fusion type. Further work is needed with clinical samples to establish whether TMPRSS2/ERG gene fusions affect radio- and chemosensitivity in vivo.

AB - PURPOSE/OBJECTIVES The androgen regulated transmembrane serine protease (TMPRSS2) and ETS transcription factor (ERG) gene fusion is a strong prognostic factor for disease recurrence following prostatectomy. Expression of TMPRSS2/ETS-related gene (ERG) fusion gene transcripts is linked with tumor proliferation, invasion, and an aggressive phenotype. The aim of this study was to define the effect of TMPRSS2/ERG fusion gene expression on chemo- and radiosensitivity in prostate tumor cell lines. MATERIALS/METHODS Clonogenic survival of PC3 and DU145 cells stably expressing TMPRSS2/ERG Types III and VI fusion genes was measured after X-irradiation (0-8Gy) and Paclitaxel. Cell cycle changes and DNA double-strand break induction and repair were assessed. Differential gene expression was measured by microarray analysis. ERG signaling pathway interactions were studied using Ariadne Pathway Studio. RESULTS Expression of the TMPRSS2/ERG fusions in PC3 cells increased radiation sensitivity and decreased paclitaxel sensitivity. Increased radiosensitivity was associated with persistent DNA breaks 24hr post-irradiation, down-regulation of genes involved in DNA repair and mitosis and up-regulation of ETV, an ETS transcription factor. However, DU145 Types III and VI demonstrated a different sensitivity phenotype and gene expression changes. Pathway analysis of ERG signaling further illustrated the variation between the PC3 and DU145 cell lines containing TMPRSS2/ERG fusions. CONCLUSIONS The effect of TMPRSS2/ERG gene fusions had differing effects on radiosensitivity and chemosensitivity depending on cell line and fusion type. Further work is needed with clinical samples to establish whether TMPRSS2/ERG gene fusions affect radio- and chemosensitivity in vivo.

KW - cell lines

KW - paclitaxel

KW - prostate

KW - radiosensitivity

KW - TMPRSS2/ERG

UR - http://www.scopus.com/inward/record.url?scp=80052080913&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052080913&partnerID=8YFLogxK

U2 - 10.1002/pros.21371

DO - 10.1002/pros.21371

M3 - Article

VL - 71

SP - 1548

EP - 1558

JO - The Prostate

JF - The Prostate

SN - 0270-4137

IS - 14

ER -