Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis

BACKGROUND Several studies have suggested that a high fat diet (HFD) may be a risk factor of prostate cancer (PCa). As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft u...

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Veröffentlicht in:The Prostate 2008-02, Vol.68 (3), p.321-335
Hauptverfasser: Narita, Shintaro, Tsuchiya, Norihiko, Saito, Mitsuru, Inoue, Takamitsu, Kumazawa, Teruaki, Yuasa, Takeshi, Nakamura, Akira, Habuchi, Tomonori
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container_end_page 335
container_issue 3
container_start_page 321
container_title The Prostate
container_volume 68
creator Narita, Shintaro
Tsuchiya, Norihiko
Saito, Mitsuru
Inoue, Takamitsu
Kumazawa, Teruaki
Yuasa, Takeshi
Nakamura, Akira
Habuchi, Tomonori
description BACKGROUND Several studies have suggested that a high fat diet (HFD) may be a risk factor of prostate cancer (PCa). As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD). METHODS LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT‐PCR experiments. As for insulin‐like growth factor I receptor (IGF‐IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens. RESULTS Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P 
doi_str_mv 10.1002/pros.20681
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As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD). METHODS LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT‐PCR experiments. As for insulin‐like growth factor I receptor (IGF‐IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens. RESULTS Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P &lt; 0.001 and P = 0.006, respectively). We found 64 up‐regulated genes (0.19%) and 14 down‐regulated genes (0.04%) with more than twofold differences in the HFD xenograft. IGF‐IR, TNFRSF, and LPL showed striking differences in the quantitative RT‐PCR experiment. Immunostaining further revealed marked enhanced IGF‐IR expression in the HFD xenograft. In human PCa, the lowest IGF‐IR immunoreactivity group tended to have the lowest body mass index in both normal and PCa epithelium. CONCLUSION HFD induced remarkable up‐ and down‐regulation of mRNA of a substantial number of genes. Furthermore, the IGF‐I system may be involved in the HFD‐associated enhanced progression of PCa. Prostate 68: 321–335, 2008. © 2008 Wiley‐Liss, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.20681</identifier><identifier>PMID: 18175332</identifier><identifier>CODEN: PRSTDS</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; Biological and medical sciences ; Dietary Fats - administration &amp; dosage ; Gene Expression Regulation, Neoplastic ; Gynecology. Andrology. Obstetrics ; high fat diet ; Humans ; Immunohistochemistry ; insulin-like growth factor I receptor ; Male ; Male genital diseases ; Medical sciences ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; microarray ; Nephrology. Urinary tract diseases ; Oligonucleotide Array Sequence Analysis ; prostate cancer ; Prostate-Specific Antigen - blood ; Prostatic Neoplasms - blood ; Prostatic Neoplasms - genetics ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Receptor, IGF Type 1 - biosynthesis ; Receptor, IGF Type 1 - genetics ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger - biosynthesis ; RNA, Messenger - genetics ; Specific Pathogen-Free Organisms ; Tumors ; Tumors of the urinary system ; Urinary tract. 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As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD). METHODS LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT‐PCR experiments. As for insulin‐like growth factor I receptor (IGF‐IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens. RESULTS Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P &lt; 0.001 and P = 0.006, respectively). We found 64 up‐regulated genes (0.19%) and 14 down‐regulated genes (0.04%) with more than twofold differences in the HFD xenograft. IGF‐IR, TNFRSF, and LPL showed striking differences in the quantitative RT‐PCR experiment. Immunostaining further revealed marked enhanced IGF‐IR expression in the HFD xenograft. In human PCa, the lowest IGF‐IR immunoreactivity group tended to have the lowest body mass index in both normal and PCa epithelium. CONCLUSION HFD induced remarkable up‐ and down‐regulation of mRNA of a substantial number of genes. Furthermore, the IGF‐I system may be involved in the HFD‐associated enhanced progression of PCa. Prostate 68: 321–335, 2008. © 2008 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Dietary Fats - administration &amp; dosage</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gynecology. Andrology. Obstetrics</subject><subject>high fat diet</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>insulin-like growth factor I receptor</subject><subject>Male</subject><subject>Male genital diseases</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>microarray</subject><subject>Nephrology. Urinary tract diseases</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>prostate cancer</subject><subject>Prostate-Specific Antigen - blood</subject><subject>Prostatic Neoplasms - blood</subject><subject>Prostatic Neoplasms - genetics</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Receptor, IGF Type 1 - biosynthesis</subject><subject>Receptor, IGF Type 1 - genetics</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - biosynthesis</subject><subject>RNA, Messenger - genetics</subject><subject>Specific Pathogen-Free Organisms</subject><subject>Tumors</subject><subject>Tumors of the urinary system</subject><subject>Urinary tract. 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Andrology. Obstetrics</topic><topic>high fat diet</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>insulin-like growth factor I receptor</topic><topic>Male</topic><topic>Male genital diseases</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>microarray</topic><topic>Nephrology. Urinary tract diseases</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>prostate cancer</topic><topic>Prostate-Specific Antigen - blood</topic><topic>Prostatic Neoplasms - blood</topic><topic>Prostatic Neoplasms - genetics</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Receptor, IGF Type 1 - biosynthesis</topic><topic>Receptor, IGF Type 1 - genetics</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - biosynthesis</topic><topic>RNA, Messenger - genetics</topic><topic>Specific Pathogen-Free Organisms</topic><topic>Tumors</topic><topic>Tumors of the urinary system</topic><topic>Urinary tract. Prostate gland</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Narita, Shintaro</creatorcontrib><creatorcontrib>Tsuchiya, Norihiko</creatorcontrib><creatorcontrib>Saito, Mitsuru</creatorcontrib><creatorcontrib>Inoue, Takamitsu</creatorcontrib><creatorcontrib>Kumazawa, Teruaki</creatorcontrib><creatorcontrib>Yuasa, Takeshi</creatorcontrib><creatorcontrib>Nakamura, Akira</creatorcontrib><creatorcontrib>Habuchi, Tomonori</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Narita, Shintaro</au><au>Tsuchiya, Norihiko</au><au>Saito, Mitsuru</au><au>Inoue, Takamitsu</au><au>Kumazawa, Teruaki</au><au>Yuasa, Takeshi</au><au>Nakamura, Akira</au><au>Habuchi, Tomonori</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2008-02-15</date><risdate>2008</risdate><volume>68</volume><issue>3</issue><spage>321</spage><epage>335</epage><pages>321-335</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><coden>PRSTDS</coden><abstract>BACKGROUND Several studies have suggested that a high fat diet (HFD) may be a risk factor of prostate cancer (PCa). As a first step to delineate the molecular mechanisms underlying the enhanced progression of PCa under HFD, we investigated the differential gene expressions of a human PCa xenograft under HFD and a low fat diet (LFD). METHODS LNCaP cells were subcutaneously injected in 20 nude mice, which were equally divided into two groups, the HFD group and LFD group. Oligonucleotide microarray analyses were performed using mice xenografts from HFD and LFD, and the results of candidate genes with a significant differential expression were validated by quantitative RT‐PCR experiments. As for insulin‐like growth factor I receptor (IGF‐IR), protein expression levels were further examined by immunohistochemistry in xenograft tissues and in 78 radical prostatectomy specimens. RESULTS Tumor volume and serum PSA levels were significantly higher in the HFD group than in the LFD group (P &lt; 0.001 and P = 0.006, respectively). We found 64 up‐regulated genes (0.19%) and 14 down‐regulated genes (0.04%) with more than twofold differences in the HFD xenograft. IGF‐IR, TNFRSF, and LPL showed striking differences in the quantitative RT‐PCR experiment. Immunostaining further revealed marked enhanced IGF‐IR expression in the HFD xenograft. In human PCa, the lowest IGF‐IR immunoreactivity group tended to have the lowest body mass index in both normal and PCa epithelium. CONCLUSION HFD induced remarkable up‐ and down‐regulation of mRNA of a substantial number of genes. Furthermore, the IGF‐I system may be involved in the HFD‐associated enhanced progression of PCa. Prostate 68: 321–335, 2008. © 2008 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>18175332</pmid><doi>10.1002/pros.20681</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Biological and medical sciences
Dietary Fats - administration & dosage
Gene Expression Regulation, Neoplastic
Gynecology. Andrology. Obstetrics
high fat diet
Humans
Immunohistochemistry
insulin-like growth factor I receptor
Male
Male genital diseases
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Nude
microarray
Nephrology. Urinary tract diseases
Oligonucleotide Array Sequence Analysis
prostate cancer
Prostate-Specific Antigen - blood
Prostatic Neoplasms - blood
Prostatic Neoplasms - genetics
Prostatic Neoplasms - metabolism
Prostatic Neoplasms - pathology
Receptor, IGF Type 1 - biosynthesis
Receptor, IGF Type 1 - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Specific Pathogen-Free Organisms
Tumors
Tumors of the urinary system
Urinary tract. Prostate gland
title Candidate genes involved in enhanced growth of human prostate cancer under high fat feeding identified by microarray analysis
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