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 language | English |
|---|---|
| Pages (from-to) | 1-13 |
| Number of pages | 13 |
| Journal | Molecular Carcinogenesis |
| Volume | 30 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 19 2001 |
Fingerprint
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 journal › Article
}
TY - JOUR
T1 - Expression of RFG/ELE1α/ARA70 in normal and malignant prostatic epithelial cell cultures and lines
T2 - Regulation by methylation and sex steroids
AU - Tekur, Seshadri
AU - Lau, Kin Mang
AU - Long, John
AU - Burnstein, Kerry L
AU - Ho, Shuk Mei
PY - 2001/2/19
Y1 - 2001/2/19
N2 - 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.
AB - 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.
KW - 4-Hydroxy-flutamide
KW - Androgen action
KW - Androgen receptor coactivator
KW - BPH-1
KW - DNA methylation
KW - DU-145
KW - Estradiol-17β
KW - Estrogen action
KW - ICI-182780
KW - LNCaP
KW - PC-3
KW - Prostate neoplasm
KW - Steroid hormone coregulator
KW - TSU-Pr1
UR - http://www.scopus.com/inward/record.url?scp=0034746440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034746440&partnerID=8YFLogxK
U2 - 10.1002/1098-2744(200101)30:1<1::AID-MC1008>3.0.CO;2-X
DO - 10.1002/1098-2744(200101)30:1<1::AID-MC1008>3.0.CO;2-X
M3 - Article
C2 - 11255259
AN - SCOPUS:0034746440
VL - 30
SP - 1
EP - 13
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 1
ER -