Expression of RFG/ELE1α/ARA70 in normal and malignant prostatic epithelial cell cultures and lines: Regulation by methylation and sex steroids

Seshadri Tekur, Kin Mang Lau, John Long, Kerry L Burnstein, Shuk Mei Ho

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

RET fused gene (RFG)/ELE1α/androgen receptor-associated protein 70(ARA70) was first found to be involved in the activation of the RET proto-oncogene in thyroid neoplasm and has recently been shown to be a ligand-dependent transcriptional coregulator for androgen receptor (AR). The functionality of RFG/ELE1α/ARA70 remains controversial, and little is known about factors regulating its expression in the prostate. Of significant interest is whether this molecule is involved in prostate carcinogenesis. Using reverse transcriptase-polymerase chain reaction semiquantitation, we compared RFG/ELE1α/ARA70 mRNA levels in four prostate cancer cell lines (LNCaP, TSU-Prl, DU-145, and PC-3) with those found in primary cultures of normal prostatic epithelial cells (PrECs). In addition, we examined the effects of androgen and antiandrogen, estrogen and antiestrogen, and a demethylating agent on RFG/ELE1α/ARA70 mRNA expression levels in AR- and AR+ PC-3 cells. Reduced levels of RFG/ELE1α/ARA70 message were observed in all four prostate cancer cell lines when compared with normal PrECs in primary cultures. RFG/ELE1α/ARA70 mRNA levels in PC-3 cells, which express both estrogen receptor subtypes, were upregulated by 17β-estradiol and inhibited by the antiestrogen ICI-182780. In PC-3(AR+) cells, which were genetically engineered to express AR, exposure to androgen upregulated RFG/ELE1α/ARA70 mRNA expression, whereas treatment with 4-hydroxyflutamide lowered expression of this transcript. Furthermore, treatment of DU-145 cells, which did not express RFG/ELE1α/ARA70 transcripts, with a demethylating agent reactivated transcription of this gene. Polymerase chain reaction analyses of monochromosomal human-rodent hybrid panels localized a putative RFG/ELE1α/ARA70 isoform on human chromosome 5q31.1-31.2. In summary, we identified sex hormones and DNA hypermethylation as regulators of RFG/ELE1α/ARA70 expression in prostate cancer cells. In addition, we found reduced levels of RFG/ELE1α/ARA70 expression in prostate cancer cell lines when compared with expression levels in normal PrECs in culture. These findings suggest that RFG/ELE1α/ARA70 may be involved prostate carcinogenesis and that it may serve as a key mediator of estrogen-androgen synergism.

Original languageEnglish
Pages (from-to)1-13
Number of pages13
JournalMolecular Carcinogenesis
Volume30
Issue number1
DOIs
StatePublished - Feb 19 2001

Fingerprint

Androgen Receptors
Methylation
Cell Culture Techniques
Epithelial Cells
Steroids
Cell Line
Genes
Proteins
Prostatic Neoplasms
Androgens
Prostate
Messenger RNA
Estrogen Receptor Modulators
Estrogens
Carcinogenesis
Androgen Antagonists
Proto-Oncogenes
Gonadal Steroid Hormones
Human Chromosomes
Reverse Transcriptase Polymerase Chain Reaction

Keywords

  • 4-Hydroxy-flutamide
  • Androgen action
  • Androgen receptor coactivator
  • BPH-1
  • DNA methylation
  • DU-145
  • Estradiol-17β
  • Estrogen action
  • ICI-182780
  • LNCaP
  • PC-3
  • Prostate neoplasm
  • Steroid hormone coregulator
  • TSU-Pr1

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology

Cite this

Expression of RFG/ELE1α/ARA70 in normal and malignant prostatic epithelial cell cultures and lines : Regulation by methylation and sex steroids. / Tekur, Seshadri; Lau, Kin Mang; Long, John; Burnstein, Kerry L; Ho, Shuk Mei.

In: Molecular Carcinogenesis, Vol. 30, No. 1, 19.02.2001, p. 1-13.

Research output: Contribution to journalArticle

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AU - Long, John

AU - Burnstein, Kerry L

AU - Ho, Shuk Mei

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KW - DU-145

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KW - Estrogen action

KW - ICI-182780

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KW - Prostate neoplasm

KW - Steroid hormone coregulator

KW - TSU-Pr1

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