Gene promoter methylation in prostate tumor-associated stromal cells

Jeffrey A. Hanson, John W. Gillespie, Amelia Grover, Michael A. Tangrea, Rodrigo F. Chuaqui, Michael R. Emmert-Buck, Joseph A. Tangrea, Stephen K. Libutti, W. Marston Linehan, Karen G. Woodson

Research output: Contribution to journalArticle

134 Citations (Scopus)

Abstract

Background: Gene expression can be silenced through the methylation of specific sites in the promoter region. This mechanism of gene silencing has an important role in the carcinogenesis of prostate and other cancers. Although tumor-associated stromal cells also exhibit changes in gene expression, promoter methylation has not been described in these cells. Methods: Tumor epithelia, tumor-associated stroma and normal epithelia, and stroma adjacent to tumor tissues were isolated from whole-mount prostatectomy specimens (two per patient) of patients (n = 5) with localized prostate cancer and from normal epithelia and stroma from benign prostate hyperplasia specimens (two per patient) from men (n = 5) without prostate cancer by using laser capture microdissection or expression microdissection. The methylation status of three genes important in prostate carcinogenesis, GSTP1, RARβ2, and CD44, were evaluated using quantitative methylation-sensitive polymerase chain reaction. Results: GSTP1 and RARβ2 were methylated in the tumor epithelium of all five prostate cancer patients and in the tumor-associated stroma in four of the five patients. CD44 was methylated in the tumor epithelium from four of the five patients but not in the tumor stroma. GSTP1 and RARβ2 were methylated in normal epithelium of two and four patients, respectively, and in normal stroma of one and two patients, respectively, that were isolated from regions adjacent to the tumors and may have resulted from a tumor-field effect; CD44 methylation was not observed in normal epithelium or stroma. In contrast, normal epithelia and stroma from benign prostate hyperplasia specimens showed no promoter methylation in GSTP1, RARβ2, or CD44. Conclusions: The observation of promoter methylation in the non-neoplastic cells of the prostate tumor microenvironment may advance our understanding of prostate cancer development and progression and lead to new diagnostic and prognostic markers and therapeutic targets.

Original languageEnglish (US)
Pages (from-to)255-261
Number of pages7
JournalJournal of the National Cancer Institute
Volume98
Issue number4
DOIs
StatePublished - Feb 15 2006
Externally publishedYes

Fingerprint

Stromal Cells
Methylation
Prostate
Epithelium
Genes
Neoplasms
Prostatic Neoplasms
Hyperplasia
Carcinogenesis
Laser Capture Microdissection
Gene Expression
Microdissection
Tumor Microenvironment
Gene Silencing
Prostatectomy
Genetic Promoter Regions
Observation
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hanson, J. A., Gillespie, J. W., Grover, A., Tangrea, M. A., Chuaqui, R. F., Emmert-Buck, M. R., ... Woodson, K. G. (2006). Gene promoter methylation in prostate tumor-associated stromal cells. Journal of the National Cancer Institute, 98(4), 255-261. https://doi.org/10.1093/jnci/djj051

Gene promoter methylation in prostate tumor-associated stromal cells. / Hanson, Jeffrey A.; Gillespie, John W.; Grover, Amelia; Tangrea, Michael A.; Chuaqui, Rodrigo F.; Emmert-Buck, Michael R.; Tangrea, Joseph A.; Libutti, Stephen K.; Linehan, W. Marston; Woodson, Karen G.

In: Journal of the National Cancer Institute, Vol. 98, No. 4, 15.02.2006, p. 255-261.

Research output: Contribution to journalArticle

Hanson, JA, Gillespie, JW, Grover, A, Tangrea, MA, Chuaqui, RF, Emmert-Buck, MR, Tangrea, JA, Libutti, SK, Linehan, WM & Woodson, KG 2006, 'Gene promoter methylation in prostate tumor-associated stromal cells', Journal of the National Cancer Institute, vol. 98, no. 4, pp. 255-261. https://doi.org/10.1093/jnci/djj051
Hanson JA, Gillespie JW, Grover A, Tangrea MA, Chuaqui RF, Emmert-Buck MR et al. Gene promoter methylation in prostate tumor-associated stromal cells. Journal of the National Cancer Institute. 2006 Feb 15;98(4):255-261. https://doi.org/10.1093/jnci/djj051
Hanson, Jeffrey A. ; Gillespie, John W. ; Grover, Amelia ; Tangrea, Michael A. ; Chuaqui, Rodrigo F. ; Emmert-Buck, Michael R. ; Tangrea, Joseph A. ; Libutti, Stephen K. ; Linehan, W. Marston ; Woodson, Karen G. / Gene promoter methylation in prostate tumor-associated stromal cells. In: Journal of the National Cancer Institute. 2006 ; Vol. 98, No. 4. pp. 255-261.
@article{dc5217c465e344be8e53bb2d3cb97f5e,
title = "Gene promoter methylation in prostate tumor-associated stromal cells",
abstract = "Background: Gene expression can be silenced through the methylation of specific sites in the promoter region. This mechanism of gene silencing has an important role in the carcinogenesis of prostate and other cancers. Although tumor-associated stromal cells also exhibit changes in gene expression, promoter methylation has not been described in these cells. Methods: Tumor epithelia, tumor-associated stroma and normal epithelia, and stroma adjacent to tumor tissues were isolated from whole-mount prostatectomy specimens (two per patient) of patients (n = 5) with localized prostate cancer and from normal epithelia and stroma from benign prostate hyperplasia specimens (two per patient) from men (n = 5) without prostate cancer by using laser capture microdissection or expression microdissection. The methylation status of three genes important in prostate carcinogenesis, GSTP1, RARβ2, and CD44, were evaluated using quantitative methylation-sensitive polymerase chain reaction. Results: GSTP1 and RARβ2 were methylated in the tumor epithelium of all five prostate cancer patients and in the tumor-associated stroma in four of the five patients. CD44 was methylated in the tumor epithelium from four of the five patients but not in the tumor stroma. GSTP1 and RARβ2 were methylated in normal epithelium of two and four patients, respectively, and in normal stroma of one and two patients, respectively, that were isolated from regions adjacent to the tumors and may have resulted from a tumor-field effect; CD44 methylation was not observed in normal epithelium or stroma. In contrast, normal epithelia and stroma from benign prostate hyperplasia specimens showed no promoter methylation in GSTP1, RARβ2, or CD44. Conclusions: The observation of promoter methylation in the non-neoplastic cells of the prostate tumor microenvironment may advance our understanding of prostate cancer development and progression and lead to new diagnostic and prognostic markers and therapeutic targets.",
author = "Hanson, {Jeffrey A.} and Gillespie, {John W.} and Amelia Grover and Tangrea, {Michael A.} and Chuaqui, {Rodrigo F.} and Emmert-Buck, {Michael R.} and Tangrea, {Joseph A.} and Libutti, {Stephen K.} and Linehan, {W. Marston} and Woodson, {Karen G.}",
year = "2006",
month = "2",
day = "15",
doi = "10.1093/jnci/djj051",
language = "English (US)",
volume = "98",
pages = "255--261",
journal = "Journal of the National Cancer Institute",
issn = "0027-8874",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Gene promoter methylation in prostate tumor-associated stromal cells

AU - Hanson, Jeffrey A.

AU - Gillespie, John W.

AU - Grover, Amelia

AU - Tangrea, Michael A.

AU - Chuaqui, Rodrigo F.

AU - Emmert-Buck, Michael R.

AU - Tangrea, Joseph A.

AU - Libutti, Stephen K.

AU - Linehan, W. Marston

AU - Woodson, Karen G.

PY - 2006/2/15

Y1 - 2006/2/15

N2 - Background: Gene expression can be silenced through the methylation of specific sites in the promoter region. This mechanism of gene silencing has an important role in the carcinogenesis of prostate and other cancers. Although tumor-associated stromal cells also exhibit changes in gene expression, promoter methylation has not been described in these cells. Methods: Tumor epithelia, tumor-associated stroma and normal epithelia, and stroma adjacent to tumor tissues were isolated from whole-mount prostatectomy specimens (two per patient) of patients (n = 5) with localized prostate cancer and from normal epithelia and stroma from benign prostate hyperplasia specimens (two per patient) from men (n = 5) without prostate cancer by using laser capture microdissection or expression microdissection. The methylation status of three genes important in prostate carcinogenesis, GSTP1, RARβ2, and CD44, were evaluated using quantitative methylation-sensitive polymerase chain reaction. Results: GSTP1 and RARβ2 were methylated in the tumor epithelium of all five prostate cancer patients and in the tumor-associated stroma in four of the five patients. CD44 was methylated in the tumor epithelium from four of the five patients but not in the tumor stroma. GSTP1 and RARβ2 were methylated in normal epithelium of two and four patients, respectively, and in normal stroma of one and two patients, respectively, that were isolated from regions adjacent to the tumors and may have resulted from a tumor-field effect; CD44 methylation was not observed in normal epithelium or stroma. In contrast, normal epithelia and stroma from benign prostate hyperplasia specimens showed no promoter methylation in GSTP1, RARβ2, or CD44. Conclusions: The observation of promoter methylation in the non-neoplastic cells of the prostate tumor microenvironment may advance our understanding of prostate cancer development and progression and lead to new diagnostic and prognostic markers and therapeutic targets.

AB - Background: Gene expression can be silenced through the methylation of specific sites in the promoter region. This mechanism of gene silencing has an important role in the carcinogenesis of prostate and other cancers. Although tumor-associated stromal cells also exhibit changes in gene expression, promoter methylation has not been described in these cells. Methods: Tumor epithelia, tumor-associated stroma and normal epithelia, and stroma adjacent to tumor tissues were isolated from whole-mount prostatectomy specimens (two per patient) of patients (n = 5) with localized prostate cancer and from normal epithelia and stroma from benign prostate hyperplasia specimens (two per patient) from men (n = 5) without prostate cancer by using laser capture microdissection or expression microdissection. The methylation status of three genes important in prostate carcinogenesis, GSTP1, RARβ2, and CD44, were evaluated using quantitative methylation-sensitive polymerase chain reaction. Results: GSTP1 and RARβ2 were methylated in the tumor epithelium of all five prostate cancer patients and in the tumor-associated stroma in four of the five patients. CD44 was methylated in the tumor epithelium from four of the five patients but not in the tumor stroma. GSTP1 and RARβ2 were methylated in normal epithelium of two and four patients, respectively, and in normal stroma of one and two patients, respectively, that were isolated from regions adjacent to the tumors and may have resulted from a tumor-field effect; CD44 methylation was not observed in normal epithelium or stroma. In contrast, normal epithelia and stroma from benign prostate hyperplasia specimens showed no promoter methylation in GSTP1, RARβ2, or CD44. Conclusions: The observation of promoter methylation in the non-neoplastic cells of the prostate tumor microenvironment may advance our understanding of prostate cancer development and progression and lead to new diagnostic and prognostic markers and therapeutic targets.

UR - http://www.scopus.com/inward/record.url?scp=33144465069&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33144465069&partnerID=8YFLogxK

U2 - 10.1093/jnci/djj051

DO - 10.1093/jnci/djj051

M3 - Article

C2 - 16478744

AN - SCOPUS:33144465069

VL - 98

SP - 255

EP - 261

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 4

ER -