Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression

Shaobo Zhang, Ming Li Hsieh, Wen Zhu, George G. Klee, Donald J. Tindall, Charles Y.F. Young

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

T 3 plays an important role in the regulation of cell growth and differentiation. In this study, we show the interactive effects of T 3 and androgens on the growth response and expression of the prostate-specific genes, PSA (prostate-specific antigen) and hK2 (human glandular kallikrein), in the human prostate cancer cell line, LNCaP. T 3 alone showed pronounced growth enhancement in a dose-dependent fashion. However, in the presence of androgens, higher concentrations of T 3 were required to produce additional proliferative effects. T 3 , androgens, or a combination of the two up- regulated PSA protein production in a dose-dependent fashion, but T 3 had little stimulator effect on hK2 protein expression, regardless of the presence or absence of androgens. Using gene transfer assays, T 3 alone showed no effect on transcriptional activation of a reporter gene mediated by the PSA or hK2 enhancer/promoters. T 3 potentiated the androgen-mediated transcription of the PSA gene but not that of the hK2 gene. A previous study suggested that the T 3 effect on PSA protein expression was caused by an up- regulation of the androgen receptor (AR) protein by T 3 . Our results contradict these. Although AR expression was increased by T 3 alone, Western blot analysis showed that the total cellular AR level was not further increased by T 3 in the presence of androgens, in comparisons with cells stimulated by androgens alone. Both Western blot analysis and a gel DNA band shift assay revealed that nuclear AR was not increased by T 3 . This study suggests that transcription factor(s) other than the AR may mediate T 3 enhancement of androgenic induction of PSA expression.

Original languageEnglish (US)
Pages (from-to)1665-1671
Number of pages7
JournalEndocrinology
Volume140
Issue number4
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Triiodothyronine
Androgens
Prostate-Specific Antigen
Prostate
Androgen Receptors
Gene Expression
Growth
Genes
Proteins
Western Blotting
Tissue Kallikreins
Cytoplasmic and Nuclear Receptors
Reporter Genes
Transcriptional Activation
Cell Differentiation
Prostatic Neoplasms
Transcription Factors
Up-Regulation
Gels
Cell Line

ASJC Scopus subject areas

  • Endocrinology

Cite this

Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression. / Zhang, Shaobo; Hsieh, Ming Li; Zhu, Wen; Klee, George G.; Tindall, Donald J.; Young, Charles Y.F.

In: Endocrinology, Vol. 140, No. 4, 01.01.1999, p. 1665-1671.

Research output: Contribution to journalArticle

Zhang, Shaobo ; Hsieh, Ming Li ; Zhu, Wen ; Klee, George G. ; Tindall, Donald J. ; Young, Charles Y.F. / Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression. In: Endocrinology. 1999 ; Vol. 140, No. 4. pp. 1665-1671.
@article{b78595954eac43c4a8aefe2fe9cff046,
title = "Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression",
abstract = "T 3 plays an important role in the regulation of cell growth and differentiation. In this study, we show the interactive effects of T 3 and androgens on the growth response and expression of the prostate-specific genes, PSA (prostate-specific antigen) and hK2 (human glandular kallikrein), in the human prostate cancer cell line, LNCaP. T 3 alone showed pronounced growth enhancement in a dose-dependent fashion. However, in the presence of androgens, higher concentrations of T 3 were required to produce additional proliferative effects. T 3 , androgens, or a combination of the two up- regulated PSA protein production in a dose-dependent fashion, but T 3 had little stimulator effect on hK2 protein expression, regardless of the presence or absence of androgens. Using gene transfer assays, T 3 alone showed no effect on transcriptional activation of a reporter gene mediated by the PSA or hK2 enhancer/promoters. T 3 potentiated the androgen-mediated transcription of the PSA gene but not that of the hK2 gene. A previous study suggested that the T 3 effect on PSA protein expression was caused by an up- regulation of the androgen receptor (AR) protein by T 3 . Our results contradict these. Although AR expression was increased by T 3 alone, Western blot analysis showed that the total cellular AR level was not further increased by T 3 in the presence of androgens, in comparisons with cells stimulated by androgens alone. Both Western blot analysis and a gel DNA band shift assay revealed that nuclear AR was not increased by T 3 . This study suggests that transcription factor(s) other than the AR may mediate T 3 enhancement of androgenic induction of PSA expression.",
author = "Shaobo Zhang and Hsieh, {Ming Li} and Wen Zhu and Klee, {George G.} and Tindall, {Donald J.} and Young, {Charles Y.F.}",
year = "1999",
month = "1",
day = "1",
doi = "10.1210/endo.140.4.6666",
language = "English (US)",
volume = "140",
pages = "1665--1671",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "4",

}

TY - JOUR

T1 - Interactive effects of triiodothyronine and androgens on prostate cell growth and gene expression

AU - Zhang, Shaobo

AU - Hsieh, Ming Li

AU - Zhu, Wen

AU - Klee, George G.

AU - Tindall, Donald J.

AU - Young, Charles Y.F.

PY - 1999/1/1

Y1 - 1999/1/1

N2 - T 3 plays an important role in the regulation of cell growth and differentiation. In this study, we show the interactive effects of T 3 and androgens on the growth response and expression of the prostate-specific genes, PSA (prostate-specific antigen) and hK2 (human glandular kallikrein), in the human prostate cancer cell line, LNCaP. T 3 alone showed pronounced growth enhancement in a dose-dependent fashion. However, in the presence of androgens, higher concentrations of T 3 were required to produce additional proliferative effects. T 3 , androgens, or a combination of the two up- regulated PSA protein production in a dose-dependent fashion, but T 3 had little stimulator effect on hK2 protein expression, regardless of the presence or absence of androgens. Using gene transfer assays, T 3 alone showed no effect on transcriptional activation of a reporter gene mediated by the PSA or hK2 enhancer/promoters. T 3 potentiated the androgen-mediated transcription of the PSA gene but not that of the hK2 gene. A previous study suggested that the T 3 effect on PSA protein expression was caused by an up- regulation of the androgen receptor (AR) protein by T 3 . Our results contradict these. Although AR expression was increased by T 3 alone, Western blot analysis showed that the total cellular AR level was not further increased by T 3 in the presence of androgens, in comparisons with cells stimulated by androgens alone. Both Western blot analysis and a gel DNA band shift assay revealed that nuclear AR was not increased by T 3 . This study suggests that transcription factor(s) other than the AR may mediate T 3 enhancement of androgenic induction of PSA expression.

AB - T 3 plays an important role in the regulation of cell growth and differentiation. In this study, we show the interactive effects of T 3 and androgens on the growth response and expression of the prostate-specific genes, PSA (prostate-specific antigen) and hK2 (human glandular kallikrein), in the human prostate cancer cell line, LNCaP. T 3 alone showed pronounced growth enhancement in a dose-dependent fashion. However, in the presence of androgens, higher concentrations of T 3 were required to produce additional proliferative effects. T 3 , androgens, or a combination of the two up- regulated PSA protein production in a dose-dependent fashion, but T 3 had little stimulator effect on hK2 protein expression, regardless of the presence or absence of androgens. Using gene transfer assays, T 3 alone showed no effect on transcriptional activation of a reporter gene mediated by the PSA or hK2 enhancer/promoters. T 3 potentiated the androgen-mediated transcription of the PSA gene but not that of the hK2 gene. A previous study suggested that the T 3 effect on PSA protein expression was caused by an up- regulation of the androgen receptor (AR) protein by T 3 . Our results contradict these. Although AR expression was increased by T 3 alone, Western blot analysis showed that the total cellular AR level was not further increased by T 3 in the presence of androgens, in comparisons with cells stimulated by androgens alone. Both Western blot analysis and a gel DNA band shift assay revealed that nuclear AR was not increased by T 3 . This study suggests that transcription factor(s) other than the AR may mediate T 3 enhancement of androgenic induction of PSA expression.

UR - http://www.scopus.com/inward/record.url?scp=0032982444&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032982444&partnerID=8YFLogxK

U2 - 10.1210/endo.140.4.6666

DO - 10.1210/endo.140.4.6666

M3 - Article

C2 - 10098501

AN - SCOPUS:0032982444

VL - 140

SP - 1665

EP - 1671

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 4

ER -