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The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer
Glycine N-methyltransferase ( GNMT ) has a role in the metabolism of methionine as well as in gluconeogenesis. It has recently been reported that the GNMT gene acts as a tumor-susceptible gene. However, little is known about the specific function of GNMT in carcinogenesis and malignant progression....
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| Published in: | Modern pathology 2011-09, Vol.24 (9), p.1272-1280 |
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| creator | Song, Yoo Hyun Shiota, Masaki Kuroiwa, Kentaro Naito, Seiji Oda, Yoshinao |
| description | Glycine N-methyltransferase
(
GNMT
) has a role in the metabolism of methionine as well as in gluconeogenesis. It has recently been reported that the
GNMT
gene acts as a tumor-susceptible gene. However, little is known about the specific function of
GNMT
in carcinogenesis and malignant progression. To better our understanding of the function of
GNMT
in prostate cancer, we used siRNAs to examine the effects of
GNMT
knockdown on cell proliferation and the cell cycle. In addition, the relation between immunohistochemical
GNMT
expression and clinicopathologic parameters was investigated in 148 prostate cancer tissues. Here, we show that siRNA-mediated
GNMT
knockdown results in an inhibition of proliferation, and induces G1 arrest and apoptosis in prostate cancer cell lines. Moreover, high cytoplasmic
GNMT
expression was also correlated with a higher Gleason score (
P |
| doi_str_mv | 10.1038/modpathol.2011.76 |
| format | article |
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(
GNMT
) has a role in the metabolism of methionine as well as in gluconeogenesis. It has recently been reported that the
GNMT
gene acts as a tumor-susceptible gene. However, little is known about the specific function of
GNMT
in carcinogenesis and malignant progression. To better our understanding of the function of
GNMT
in prostate cancer, we used siRNAs to examine the effects of
GNMT
knockdown on cell proliferation and the cell cycle. In addition, the relation between immunohistochemical
GNMT
expression and clinicopathologic parameters was investigated in 148 prostate cancer tissues. Here, we show that siRNA-mediated
GNMT
knockdown results in an inhibition of proliferation, and induces G1 arrest and apoptosis in prostate cancer cell lines. Moreover, high cytoplasmic
GNMT
expression was also correlated with a higher Gleason score (
P
<0.001) and higher pT stage (
P
=0.027). The patients with high
GNMT
cytoplasmic expression showed significantly lower disease-free survival rates than patients with low expression (
P
<0.001). High
GNMT
cytoplasmic expression had a significant impact on patient disease-free survival in multivariate analysis (
P
=0.005). This is the first investigation to reveal the novel finding that
GNMT
may have an important role in promoting prostate cancer cell growth via the regulation of apoptosis and contribute to the progression of prostate cancer. The modulation of
GNMT
expression or function may be a strategy for developing novel therapeutics for prostate cancer.
GNMT
may represent a novel marker of malignant progression and poor prognosis in prostate cancer.</description><identifier>ISSN: 0893-3952</identifier><identifier>EISSN: 1530-0285</identifier><identifier>DOI: 10.1038/modpathol.2011.76</identifier><identifier>PMID: 21572396</identifier><identifier>CODEN: MODPEO</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/45/612/1238 ; 692/420/755 ; 692/699/67/589/466 ; Aged ; Antibodies ; Apoptosis ; Biomarkers, Tumor - analysis ; Blotting, Western ; Cell cycle ; Cell Cycle - physiology ; Cell growth ; Cell Line, Tumor ; Cell Proliferation ; Cell Separation ; Disease Progression ; Flow Cytometry ; Gene Knockdown Techniques ; Glycine N-Methyltransferase - metabolism ; Humans ; Laboratory Medicine ; Liver cancer ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Metabolism ; Metabolites ; Middle Aged ; Neoplasm Staging ; original-article ; Pathology ; Prognosis ; Prostate cancer ; Prostatic Neoplasms - enzymology ; Prostatic Neoplasms - pathology ; Proteins ; RNA, Small Interfering</subject><ispartof>Modern pathology, 2011-09, Vol.24 (9), p.1272-1280</ispartof><rights>United States and Canadian Academy of Pathology, Inc. 2011</rights><rights>Copyright Nature Publishing Group Sep 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-b9ba326c751034839e2fc46a5cec5037e2e8386ce5f537cb1c31ddab1a8b64083</citedby><cites>FETCH-LOGICAL-c479t-b9ba326c751034839e2fc46a5cec5037e2e8386ce5f537cb1c31ddab1a8b64083</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21572396$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Yoo Hyun</creatorcontrib><creatorcontrib>Shiota, Masaki</creatorcontrib><creatorcontrib>Kuroiwa, Kentaro</creatorcontrib><creatorcontrib>Naito, Seiji</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><title>The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer</title><title>Modern pathology</title><addtitle>Mod Pathol</addtitle><addtitle>Mod Pathol</addtitle><description>Glycine N-methyltransferase
(
GNMT
) has a role in the metabolism of methionine as well as in gluconeogenesis. It has recently been reported that the
GNMT
gene acts as a tumor-susceptible gene. However, little is known about the specific function of
GNMT
in carcinogenesis and malignant progression. To better our understanding of the function of
GNMT
in prostate cancer, we used siRNAs to examine the effects of
GNMT
knockdown on cell proliferation and the cell cycle. In addition, the relation between immunohistochemical
GNMT
expression and clinicopathologic parameters was investigated in 148 prostate cancer tissues. Here, we show that siRNA-mediated
GNMT
knockdown results in an inhibition of proliferation, and induces G1 arrest and apoptosis in prostate cancer cell lines. Moreover, high cytoplasmic
GNMT
expression was also correlated with a higher Gleason score (
P
<0.001) and higher pT stage (
P
=0.027). The patients with high
GNMT
cytoplasmic expression showed significantly lower disease-free survival rates than patients with low expression (
P
<0.001). High
GNMT
cytoplasmic expression had a significant impact on patient disease-free survival in multivariate analysis (
P
=0.005). This is the first investigation to reveal the novel finding that
GNMT
may have an important role in promoting prostate cancer cell growth via the regulation of apoptosis and contribute to the progression of prostate cancer. The modulation of
GNMT
expression or function may be a strategy for developing novel therapeutics for prostate cancer.
GNMT
may represent a novel marker of malignant progression and poor prognosis in prostate cancer.</description><subject>631/45/612/1238</subject><subject>692/420/755</subject><subject>692/699/67/589/466</subject><subject>Aged</subject><subject>Antibodies</subject><subject>Apoptosis</subject><subject>Biomarkers, Tumor - analysis</subject><subject>Blotting, Western</subject><subject>Cell cycle</subject><subject>Cell Cycle - physiology</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Cell Separation</subject><subject>Disease Progression</subject><subject>Flow Cytometry</subject><subject>Gene Knockdown Techniques</subject><subject>Glycine N-Methyltransferase - metabolism</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Liver cancer</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Metabolism</subject><subject>Metabolites</subject><subject>Middle Aged</subject><subject>Neoplasm Staging</subject><subject>original-article</subject><subject>Pathology</subject><subject>Prognosis</subject><subject>Prostate cancer</subject><subject>Prostatic Neoplasms - enzymology</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Proteins</subject><subject>RNA, Small Interfering</subject><issn>0893-3952</issn><issn>1530-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNp1kEtPwzAQhC0EoqXwA7igiHuKH3HiHFHFS6rgUs6W42zSVIkdbPfQf4-jFjhxWln7zcx6ELoleEkwEw-DrUcVtrZfUkzIssjP0JxwhlNMBT9HcyxKlrKS0xm68n6HMcm4oJdoRgkvKCvzOdpttpB0w2hdUCYkzvaQ2CZp-4PuDCTv6QBhe-iDU8Y34JSPtElCFGnlImJbMOA7nyhTJ6OzrQPvO2smk_j0QYUJNRrcNbpoVO_h5jQX6PP5abN6TdcfL2-rx3Wqs6IMaVVWitFcFzz-MROsBNroLFdcg-aYFUBBMJFr4A1nha6IZqSuVUWUqPIMC7ZA90ffmP-1Bx_kzu6diZFSCEHLDEebBSJHSMcjvYNGjq4blDtIguVUrvwtV07lyiKPmruT8b4aoP5V_LQZAXoEfFyZFtxf8v-u39Kcix0</recordid><startdate>20110901</startdate><enddate>20110901</enddate><creator>Song, Yoo Hyun</creator><creator>Shiota, Masaki</creator><creator>Kuroiwa, Kentaro</creator><creator>Naito, Seiji</creator><creator>Oda, Yoshinao</creator><general>Nature Publishing Group US</general><general>Elsevier Limited</general><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>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20110901</creationdate><title>The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer</title><author>Song, Yoo Hyun ; Shiota, Masaki ; Kuroiwa, Kentaro ; Naito, Seiji ; Oda, Yoshinao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-b9ba326c751034839e2fc46a5cec5037e2e8386ce5f537cb1c31ddab1a8b64083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>631/45/612/1238</topic><topic>692/420/755</topic><topic>692/699/67/589/466</topic><topic>Aged</topic><topic>Antibodies</topic><topic>Apoptosis</topic><topic>Biomarkers, Tumor - analysis</topic><topic>Blotting, Western</topic><topic>Cell cycle</topic><topic>Cell Cycle - physiology</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Cell Separation</topic><topic>Disease Progression</topic><topic>Flow Cytometry</topic><topic>Gene Knockdown Techniques</topic><topic>Glycine N-Methyltransferase - metabolism</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Liver cancer</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Metabolism</topic><topic>Metabolites</topic><topic>Middle Aged</topic><topic>Neoplasm Staging</topic><topic>original-article</topic><topic>Pathology</topic><topic>Prognosis</topic><topic>Prostate cancer</topic><topic>Prostatic Neoplasms - enzymology</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Proteins</topic><topic>RNA, Small Interfering</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Yoo Hyun</creatorcontrib><creatorcontrib>Shiota, Masaki</creatorcontrib><creatorcontrib>Kuroiwa, Kentaro</creatorcontrib><creatorcontrib>Naito, Seiji</creatorcontrib><creatorcontrib>Oda, Yoshinao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><jtitle>Modern pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Yoo Hyun</au><au>Shiota, Masaki</au><au>Kuroiwa, Kentaro</au><au>Naito, Seiji</au><au>Oda, Yoshinao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer</atitle><jtitle>Modern pathology</jtitle><stitle>Mod Pathol</stitle><addtitle>Mod Pathol</addtitle><date>2011-09-01</date><risdate>2011</risdate><volume>24</volume><issue>9</issue><spage>1272</spage><epage>1280</epage><pages>1272-1280</pages><issn>0893-3952</issn><eissn>1530-0285</eissn><coden>MODPEO</coden><abstract>Glycine N-methyltransferase
(
GNMT
) has a role in the metabolism of methionine as well as in gluconeogenesis. It has recently been reported that the
GNMT
gene acts as a tumor-susceptible gene. However, little is known about the specific function of
GNMT
in carcinogenesis and malignant progression. To better our understanding of the function of
GNMT
in prostate cancer, we used siRNAs to examine the effects of
GNMT
knockdown on cell proliferation and the cell cycle. In addition, the relation between immunohistochemical
GNMT
expression and clinicopathologic parameters was investigated in 148 prostate cancer tissues. Here, we show that siRNA-mediated
GNMT
knockdown results in an inhibition of proliferation, and induces G1 arrest and apoptosis in prostate cancer cell lines. Moreover, high cytoplasmic
GNMT
expression was also correlated with a higher Gleason score (
P
<0.001) and higher pT stage (
P
=0.027). The patients with high
GNMT
cytoplasmic expression showed significantly lower disease-free survival rates than patients with low expression (
P
<0.001). High
GNMT
cytoplasmic expression had a significant impact on patient disease-free survival in multivariate analysis (
P
=0.005). This is the first investigation to reveal the novel finding that
GNMT
may have an important role in promoting prostate cancer cell growth via the regulation of apoptosis and contribute to the progression of prostate cancer. The modulation of
GNMT
expression or function may be a strategy for developing novel therapeutics for prostate cancer.
GNMT
may represent a novel marker of malignant progression and poor prognosis in prostate cancer.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>21572396</pmid><doi>10.1038/modpathol.2011.76</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Modern pathology, 2011-09, Vol.24 (9), p.1272-1280 |
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| language | eng |
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| source | Nature Journals Online |
| subjects | 631/45/612/1238 692/420/755 692/699/67/589/466 Aged Antibodies Apoptosis Biomarkers, Tumor - analysis Blotting, Western Cell cycle Cell Cycle - physiology Cell growth Cell Line, Tumor Cell Proliferation Cell Separation Disease Progression Flow Cytometry Gene Knockdown Techniques Glycine N-Methyltransferase - metabolism Humans Laboratory Medicine Liver cancer Male Medical prognosis Medicine Medicine & Public Health Metabolism Metabolites Middle Aged Neoplasm Staging original-article Pathology Prognosis Prostate cancer Prostatic Neoplasms - enzymology Prostatic Neoplasms - pathology Proteins RNA, Small Interfering |
| title | The important role of glycine N-methyltransferase in the carcinogenesis and progression of prostate cancer |
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