Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia

Gangyi Dong, Roopmathy Rajah, Thanh Vu, Andrew R. Hoffman, Ronald (Ron) Rosenfeld, Charles Roberts, Donna M. Peehl, Pinchas Cohen

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT- 1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0 -20% of normal, mean 14% of normal, P <0.01). The expression of both the IGF-1R (300% of normal, P <0.05) and IGF-II (1000% of normal, P <0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.

Original languageEnglish (US)
Pages (from-to)2198-2203
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume82
Issue number7
DOIs
StatePublished - 1997

Fingerprint

Wilms' Tumor Genes
IGF Type 2 Receptor
IGF Type 1 Receptor
Prostatic Hyperplasia
Somatomedins
Stromal Cells
Tumors
Intercellular Signaling Peptides and Proteins
Genes
Insulin
Gene expression
Gene Expression
Messenger RNA
Insulin-Like Growth Factor II
Cell proliferation
Cell growth
Ribonucleases
Tumor Suppressor Genes
Insulin-Like Growth Factor I
Cell culture

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia. / Dong, Gangyi; Rajah, Roopmathy; Vu, Thanh; Hoffman, Andrew R.; Rosenfeld, Ronald (Ron); Roberts, Charles; Peehl, Donna M.; Cohen, Pinchas.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 82, No. 7, 1997, p. 2198-2203.

Research output: Contribution to journalArticle

@article{a7ea0f7529574a1589fa8e181f8cd947,
title = "Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia",
abstract = "Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT- 1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0 -20{\%} of normal, mean 14{\%} of normal, P <0.01). The expression of both the IGF-1R (300{\%} of normal, P <0.05) and IGF-II (1000{\%} of normal, P <0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.",
author = "Gangyi Dong and Roopmathy Rajah and Thanh Vu and Hoffman, {Andrew R.} and Rosenfeld, {Ronald (Ron)} and Charles Roberts and Peehl, {Donna M.} and Pinchas Cohen",
year = "1997",
doi = "10.1210/jc.82.7.2198",
language = "English (US)",
volume = "82",
pages = "2198--2203",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "7",

}

TY - JOUR

T1 - Decreased expression of Wilms' tumor gene WT-1 and elevated expression of insulin growth factor-II (IGF-II) and type 1 IGF receptor genes in prostatic stromal cells from patients with benign prostatic hyperplasia

AU - Dong, Gangyi

AU - Rajah, Roopmathy

AU - Vu, Thanh

AU - Hoffman, Andrew R.

AU - Rosenfeld, Ronald (Ron)

AU - Roberts, Charles

AU - Peehl, Donna M.

AU - Cohen, Pinchas

PY - 1997

Y1 - 1997

N2 - Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT- 1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0 -20% of normal, mean 14% of normal, P <0.01). The expression of both the IGF-1R (300% of normal, P <0.05) and IGF-II (1000% of normal, P <0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.

AB - Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. We have previously documented that the insulin-like growth factor (IGF) axis is critical for prostate cell growth and is abnormal in BPH. The type 1 IGF receptor (IGF-1R) is constitutively expressed by most body tissues and plays a significant role in regulating cell proliferation, consistent with the role of its ligands (IGF-I and IGF-II) as important mitogenic factors. The Wilms' tumor gene product (WT-1) is a tumor suppressor that has been shown to be altered in rare kidney tumors and is known to regulate IGF-II and IGF-1R. We investigated the possibility that the expression of prostatic WT-1, IGF-1R, and IGF-II genes is altered in patients with BPH. We utilized primary cultures of prostatic stromal cells grown from normal (n = 9) and hyperplastic (n = 9) surgical specimens and analyzed WT- 1, IGF-1R, and IGF-II messenger RNA levels. In all of the BPH cell strains, WT-1 expression (measured by RT-PCR and RNase protection assays) was strikingly lower than that found in normal strains (0 -20% of normal, mean 14% of normal, P <0.01). The expression of both the IGF-1R (300% of normal, P <0.05) and IGF-II (1000% of normal, P <0.01) messenger RNAs was higher in BPH strains as compared with normal strains. No changes were seen in stromal cell strains derived from prostatic adenocarcinoma. Thus, in cultured human prostatic stromal cell strains from patients with BPH, decreased WT-1 gene expression is associated with increases in the expression of the IGF-1R and IGF-II genes that are known transcriptional targets of WT-1. These findings indicate that reduced expression of the WT-1 tumor suppressor gene and elevated IGF-1R and IGF-II gene expression may be involved in the pathophysiology of prostatic hyperplasia, implying a new role for the Wilms' tumor gene in nonmalignant states.

UR - http://www.scopus.com/inward/record.url?scp=0030839835&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030839835&partnerID=8YFLogxK

U2 - 10.1210/jc.82.7.2198

DO - 10.1210/jc.82.7.2198

M3 - Article

C2 - 9215294

AN - SCOPUS:0030839835

VL - 82

SP - 2198

EP - 2203

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 7

ER -