Carcinogenesis Advance Access published online on January 20, 2005
Carcinogenesis, doi:10.1093/carcin/bgi021
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1 Department of Urology, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905; Department of Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905; Department of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, P.R.China, 250012
* To whom correspondence should be addressed. The transactivation function of the human androgen receptor (AR) can be regulated by several co-regulators that may be either positive or negative. Ubiquitous transcription factor Sp1 not only regulates the basal expression of the AR but also acts as its co-regulator. Our previous study has shown that quercetin, one of the main polyphenols, can effectively inhibit the expression and function of the AR. The present study is to address if quercetin may affect Sp1's function on AR transactivation activity in human prostate adenocarcinoma cell lines, LNCaP and PC-3. First we showed that indeed in transient transfections Sp1 could enhance transcriptional activity of the AR promoter and of androgen up-regulated gene promoters, i.e., the prostate-specific antigen and the hK2 genes. Interestingly, the enhancing activity of Sp1 could be repressed by quercetin. The gel shift and western blot analyses indicated that the specific DNA motif binding activity of Sp1 and its protein levels were not altered by quercetin. However, the state of interaction of Sp1 with the AR treated by quercetin plus androgen was different from that by androgen treatment or none as demonstrated by co-immunoprecipitation experiments and GST pull-down assays. Moreover, we showed that quercetin caused changes in post-translational modification of AR protein. The above findings strongly suggest that changes induced by quercetin in post-translational modification of the AR and in states of physical interaction of Sp1 with the AR may be critical for the attenuation of AR's function.
Received September 21, 2004
Revised December 14, 2004
Accepted January 8, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Involvement of transcription factor Sp1 in quercetin-mediated inhibitory effect on the androgen receptor in human prostate cancer cells
2 Department of Urology, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905; Department of Biochemistry and Molecular Biology, Mayo Graduate School, Mayo Clinic, Rochester, MN 55905
Charles Y. F. Young, E-mail: YOUNG.CHARLES{at}MAYO.EDU
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