Triiodothyronine modulates cell proliferation of human prostatic carcinoma cells by downregulation of the B-cell translocation gene 2

Ke Hung Tsui, Wen Chi Hsieh, Mei Hsien Lin, Phei Lang Chang, Horng Heng Juang

Research output: Contribution to journalArticlepeer-review

62 Citations (Scopus)

Abstract

BACKGROUND. Studies suggest that triiodothyronine (T3) and cognate nuclear receptors (hTR) are involved in regulation of prostatic cell growth and differentiation. To probe mechanisms for T3 effects, we studied prostate carcinoma cells, investigating the effect of T3 on expression of the B-cell translocation gene 2 (BTG2), which regulates the G1/S transition of the cell cycle. METHODS. Effects of T3 on cell proliferation were determined by 3H-thymidine incorporation. T3 modulation of BTG2 expression was investigated using immunoblots, Northern blots, and transient gene expression assays. The putative T3 response element was determined by electrophoretic mobility shift assay. RESULTS. T3 (0.1-1,000 nM) enhanced threefold the proliferation of prostate carcinoma cells and human androgen-dependent prostate carcinoma cells (LNCaP), but not PC-3 cells. T3 also inhibited BTG2 gene expression in LNCaP cells. Reporter assays showed that T3 downregulates by 50% promoter activity of the BTG2 gene in LNCaP cells but not PC-3 cells or thyroid-hormone receptor (TRβ1)-overexpression PC-3 cells. Deleting the putative thyroid hormone response element (TRE; AGCGATGACCTCAGCG) blocked the inhibitory effect of T3 on BTG2 promoter activity. Electrophoretic mobility shift assays with purified TRβ1 from in vitro translation, or with nuclear extracts from LNCaP cells and PC-3 cells, demonstrated the presence of T3 receptor binding sites in the TRE region. CONCLUSIONS. These results suggested that the T3 upregulates proliferation of LNCaP cells by downregulating BTG2 gene expression through the consensus TRE pathway.

Original languageEnglish
Pages (from-to)610-619
Number of pages10
JournalProstate
Volume68
Issue number6
DOIs
Publication statusPublished - May 2008
Externally publishedYes

Keywords

  • BTG2
  • LNCaP
  • PC-3
  • Proliferation
  • TRE
  • Triiodothyronine

ASJC Scopus subject areas

  • Oncology
  • Urology

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