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Prevention Research 5: Biological and Biochemical Mechanisms in Prevention 2

Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers

Yan Dong, Hai Wang, Haitao Zhang, James R. Marshall and Clement Ip
Yan Dong
Roswell Park Cancer Institute, Buffalo, NY
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Hai Wang
Roswell Park Cancer Institute, Buffalo, NY
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Haitao Zhang
Roswell Park Cancer Institute, Buffalo, NY
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James R. Marshall
Roswell Park Cancer Institute, Buffalo, NY
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Clement Ip
Roswell Park Cancer Institute, Buffalo, NY
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DOI:  Published May 2005
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Proc Amer Assoc Cancer Res, Volume 46, 2005

Abstract

2445

Our previous report showed that methylseleninic acid (MSA) significantly decreases the expression of androgen receptor (AR) and prostate specific antigen (PSA) in LNCaP cells (Cancer Res. 64: 19-22, 2004). The present study extended the above observations by demonstrating that the reduced availability of AR plays a key role in mediating MSA inhibition of prostate cancer cell growth and cancer-specific biomarkers. There are several lines of evidence to support our conclusion. First, by using the ARE-luciferase reporter gene assay, we found that MSA suppression of AR trans-activation could be accounted for primarily by the low AR protein level. Second, MSA inhibition of PSA and kallikrein 2 expression (two known AR-regulated genes customarily associated with prostate cancer progression) was greatly attenuated by AR overexpression. Third, transfection of AR in LNCaP cells similarly weakened the inhibitory effect of MSA on cell growth. When we used the green fluorescent protein method to select for the cells that were successfully transfected with AR, we discovered that the anti-proliferative effect of MSA was largely negated in this subset. AR signaling has been extensively documented to play an important role in the development of both androgen-dependent and -independent prostate cancer. Given our finding that MSA reduced AR availability by blocking AR transcription (rather than by increasing mRNA degradation), our study is providing justification for a mechanism-driven intervention strategy in using selenium to control prostate cancer progression.

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Cancer Research: 65 (9 Supplement)
May 2005
Volume 65, Issue 9 Supplement
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Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers
Yan Dong, Hai Wang, Haitao Zhang, James R. Marshall and Clement Ip
Cancer Res May 1 2005 (65) (9 Supplement) 573-574;

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Androgen receptor signaling intensity is a key factor in determining the sensitivity of prostate cancer cells to selenium inhibition of growth and cancer-specific biomarkers
Yan Dong, Hai Wang, Haitao Zhang, James R. Marshall and Clement Ip
Cancer Res May 1 2005 (65) (9 Supplement) 573-574;
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Show more Prevention Research 5: Biological and Biochemical Mechanisms in Prevention 2
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Cancer Research Online ISSN: 1538-7445
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