Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: Identification of novel targets
Many studies have correlated the consumption of soy‐rich diets with a decreased risk of developing hormone‐dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybean and soy foods. To better understand the molecular...
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| Veröffentlicht in: | Molecular carcinogenesis 2004-10, Vol.41 (2), p.108-119 |
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| container_title | Molecular carcinogenesis |
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| creator | Takahashi, Yoko Lavigne, Jackie A. Hursting, Stephen D. Chandramouli, Gadisetti V.R. Perkins, Susan N. Barrett, J. Carl Wang, Thomas T.Y. |
| description | Many studies have correlated the consumption of soy‐rich diets with a decreased risk of developing hormone‐dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybean and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we used a DNA microarray approach to examine the effects of genistein at concentrations in the physiologic range on global gene expression patterns in androgen‐responsive cancer cells. Microarray analyses were performed on androgen‐responsive LNCaP human prostate cancer cells exposed to 0, 1, 5, or 25 μM genistein. We found a concentration‐dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor (AR)‐mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we propose that the regulation of AR‐mediated pathways is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels. Published 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/mc.20045 |
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Carl ; Wang, Thomas T.Y.</creator><creatorcontrib>Takahashi, Yoko ; Lavigne, Jackie A. ; Hursting, Stephen D. ; Chandramouli, Gadisetti V.R. ; Perkins, Susan N. ; Barrett, J. Carl ; Wang, Thomas T.Y.</creatorcontrib><description>Many studies have correlated the consumption of soy‐rich diets with a decreased risk of developing hormone‐dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybean and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we used a DNA microarray approach to examine the effects of genistein at concentrations in the physiologic range on global gene expression patterns in androgen‐responsive cancer cells. Microarray analyses were performed on androgen‐responsive LNCaP human prostate cancer cells exposed to 0, 1, 5, or 25 μM genistein. We found a concentration‐dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor (AR)‐mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we propose that the regulation of AR‐mediated pathways is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels. 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Carl</creatorcontrib><creatorcontrib>Wang, Thomas T.Y.</creatorcontrib><title>Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: Identification of novel targets</title><title>Molecular carcinogenesis</title><addtitle>Mol. Carcinog</addtitle><description>Many studies have correlated the consumption of soy‐rich diets with a decreased risk of developing hormone‐dependent cancers, including prostate cancer. Genistein is a candidate prostate cancer preventive phytochemical found at high levels in soybean and soy foods. To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we used a DNA microarray approach to examine the effects of genistein at concentrations in the physiologic range on global gene expression patterns in androgen‐responsive cancer cells. Microarray analyses were performed on androgen‐responsive LNCaP human prostate cancer cells exposed to 0, 1, 5, or 25 μM genistein. We found a concentration‐dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor (AR)‐mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we propose that the regulation of AR‐mediated pathways is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels. Published 2004 Wiley‐Liss, Inc.</description><subject>Anticarcinogenic Agents - pharmacology</subject><subject>Cell Cycle</subject><subject>DNA Damage</subject><subject>genistein</subject><subject>Genistein - administration & dosage</subject><subject>Genistein - pharmacology</subject><subject>Humans</subject><subject>Insulin-Like Growth Factor I</subject><subject>isoflavone</subject><subject>Male</subject><subject>microarray</subject><subject>Neoplasms, Hormone-Dependent - metabolism</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>phytochemical</subject><subject>prostate cancer</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - prevention & control</subject><subject>Receptors, Androgen - metabolism</subject><subject>Receptors, Cytoplasmic and Nuclear</subject><subject>Signal Transduction</subject><subject>Stress, Physiological</subject><subject>Transcription Factors</subject><subject>Tumor Cells, Cultured</subject><issn>0899-1987</issn><issn>1098-2744</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMtu1DAUQC0EokNB4guQV4hNil9JbHbVAKWjoXRBBTvLcW4GQ2JPbU9hPoM_xmEGWCFZsnR17tHVQegpJWeUEPZysmeMEFHfQwtKlKxYK8R9tCBSqYoq2Z6gRyl9JYTStiYP0QmteSsboRbo501yfoNfX53jydkYTIxmj4034z5BwjlgGHfW9SYDzl8AwzCAzQmHAW_Au5TBeVye8X0MZVJFSNvgk7sDvI0h5XnRGm8hYgvjmF7hyx58doOzJrvgZ5MPdzDibOIGcnqMHgxmTPDk-J-im7dvPi7fVesPF5fL83Vlec3qqlG2J7TpGsFFC9Ap3ksmZVemHJSVxjABdacGa1gt-VCSSMt7xnvBGyIIP0XPD95y5u0OUtaTS_OJxkPYJV1StVLWrIAvDmDJk1KEQW-jm0zca0r0nF9PVv_OX9BnR-eum6D_Bx57F6A6AN_dCPv_ivT75R_hkZ9L__jLm_hNNy1va_3p6kJfrz7z9Wql9DX_Bap_n5M</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Takahashi, Yoko</creator><creator>Lavigne, Jackie A.</creator><creator>Hursting, Stephen D.</creator><creator>Chandramouli, Gadisetti V.R.</creator><creator>Perkins, Susan N.</creator><creator>Barrett, J. Carl</creator><creator>Wang, Thomas T.Y.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TM</scope></search><sort><creationdate>200410</creationdate><title>Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: Identification of novel targets</title><author>Takahashi, Yoko ; Lavigne, Jackie A. ; Hursting, Stephen D. ; Chandramouli, Gadisetti V.R. ; Perkins, Susan N. ; Barrett, J. Carl ; Wang, Thomas T.Y.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3525-69cd016b64347eeb93d8288bcd03e9c8aa24e5b9fca2583f2748c3d23d4360403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Anticarcinogenic Agents - pharmacology</topic><topic>Cell Cycle</topic><topic>DNA Damage</topic><topic>genistein</topic><topic>Genistein - administration & dosage</topic><topic>Genistein - pharmacology</topic><topic>Humans</topic><topic>Insulin-Like Growth Factor I</topic><topic>isoflavone</topic><topic>Male</topic><topic>microarray</topic><topic>Neoplasms, Hormone-Dependent - metabolism</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>phytochemical</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - prevention & control</topic><topic>Receptors, Androgen - metabolism</topic><topic>Receptors, Cytoplasmic and Nuclear</topic><topic>Signal Transduction</topic><topic>Stress, Physiological</topic><topic>Transcription Factors</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takahashi, Yoko</creatorcontrib><creatorcontrib>Lavigne, Jackie A.</creatorcontrib><creatorcontrib>Hursting, Stephen D.</creatorcontrib><creatorcontrib>Chandramouli, Gadisetti V.R.</creatorcontrib><creatorcontrib>Perkins, Susan N.</creatorcontrib><creatorcontrib>Barrett, J. 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To better understand the molecular mechanisms underlying the beneficial effects of genistein on prostate cancer prevention, we used a DNA microarray approach to examine the effects of genistein at concentrations in the physiologic range on global gene expression patterns in androgen‐responsive cancer cells. Microarray analyses were performed on androgen‐responsive LNCaP human prostate cancer cells exposed to 0, 1, 5, or 25 μM genistein. We found a concentration‐dependent modulation of multiple cellular pathways that are important in prostate carcinogenesis. Interestingly, the androgen receptor (AR)‐mediated pathways, in particular, appeared to be modulated by genistein at the lowest concentrations. Based on these results, we propose that the regulation of AR‐mediated pathways is potentially the most relevant chemopreventive mechanism for genistein administered at physiologic levels. 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| subjects | Anticarcinogenic Agents - pharmacology Cell Cycle DNA Damage genistein Genistein - administration & dosage Genistein - pharmacology Humans Insulin-Like Growth Factor I isoflavone Male microarray Neoplasms, Hormone-Dependent - metabolism Oligonucleotide Array Sequence Analysis phytochemical prostate cancer Prostatic Neoplasms - metabolism Prostatic Neoplasms - prevention & control Receptors, Androgen - metabolism Receptors, Cytoplasmic and Nuclear Signal Transduction Stress, Physiological Transcription Factors Tumor Cells, Cultured |
| title | Using DNA microarray analyses to elucidate the effects of genistein in androgen-responsive prostate cancer cells: Identification of novel targets |
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