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Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast
In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influ...
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| Published in: | Molecular and cellular biochemistry 2012-02, Vol.361 (1-2), p.189-195 |
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| container_title | Molecular and cellular biochemistry |
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| creator | Naushad, Shaik Mohammad Prayaga, Aruna Digumarti, Raghunadha Rao Gottumukkala, Suryanarayana Raju Kutala, Vijay Kumar |
| description | In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2′deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR–RFLP and PCR–AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08,
P
|
| doi_str_mv | 10.1007/s11010-011-1103-z |
| format | article |
| fullrecord | <record><control><sourceid>gale_proqu</sourceid><recordid>TN_cdi_proquest_miscellaneous_913032720</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A358998688</galeid><sourcerecordid>A358998688</sourcerecordid><originalsourceid>FETCH-LOGICAL-c610t-1a24f3717bed60a608e0912e960686b8054f035c216c400aed0d57e9a6cc97c13</originalsourceid><addsrcrecordid>eNp9ksFu1DAQhiMEokvhAbggCw6UQ9oZOxvHx24pUKkCDnC2HGeyckmcrZ2s2D4NB56EJ8OrFBAIkA-27O__PTP6s-wxwjECyJOICAg5IObpJPKbO9kCl1LkhUJ1N1uAAMgrlPIgexDjFSQ4sfezA46qklyUi-zrynY5PzEN-WHrwhTZOa4Yqm9fPr00ufMjBWNH59dsE4aRnGeCHa3eXrwXLxh93gSK0Q2eucho49bkaXTWdN2OBVpPnRmpYfWODZ5ya0KdyJ5GUw-diz1LZs5vTXRbYs1kR2ap61jirPNDb9jQsjqQiePD7F5rukiPbvfD7OOr8w9nb_LLd68vzk4vc1sijDkaXrRCoqypKcGUUBEo5KRKKKuyrmBZtCCWlmNpCwBDDTRLScqU1ippURxmz2ff1Ov1RHHUvYv7ooynYYpaoQDBJYdEHv2XxEIozlXBi4Q-_QO9GqbgUx_Jj1cIstz__GyG1qYj7Xw7jGnue099KpaVUlVZVYk6_guVVkO9s2nIrUv3vwlwFtgwxBio1ZvgehN2GkHvI6TnCOkUC72PkL5Jmie39U51T81PxY_MJIDPQExPfk3hV0P_dv0OZnDQFQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>912810761</pqid></control><display><type>article</type><title>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast</title><source>Springer Nature</source><creator>Naushad, Shaik Mohammad ; Prayaga, Aruna ; Digumarti, Raghunadha Rao ; Gottumukkala, Suryanarayana Raju ; Kutala, Vijay Kumar</creator><creatorcontrib>Naushad, Shaik Mohammad ; Prayaga, Aruna ; Digumarti, Raghunadha Rao ; Gottumukkala, Suryanarayana Raju ; Kutala, Vijay Kumar</creatorcontrib><description>In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2′deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR–RFLP and PCR–AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08,
P
< 0.0001). COBRA analysis confirmed hypomethylation of BNIP3 promoter CpG island in these cases. CIMP phenotype of BNIP3 showed positive association with tubule formation (
P
= 0.034) and methionine synthase reductase (MTRR) A66G (
P
= 0.002); inverse association with cytosolic serine hydroxyl methyltransferase (cSHMT) C1420T (
P
< 0.005) and 8-oxodG (<10% vs. >10% methylation: 7.24 ± 2.77 ng/ml vs. 4.42 ± 2.93 ng/ml,
P
< 0.0005); and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (
P
< 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer.</description><identifier>ISSN: 0300-8177</identifier><identifier>EISSN: 1573-4919</identifier><identifier>DOI: 10.1007/s11010-011-1103-z</identifier><identifier>PMID: 21987236</identifier><language>eng</language><publisher>Boston: Springer US</publisher><subject>5-Methyltetrahydrofolate-homocysteine S-methyltransferase ; Adenovirus ; Adenoviruses ; Amplified Fragment Length Polymorphism Analysis ; Analysis ; Biochemistry ; Biomedical and Life Sciences ; Breast cancer ; Breast Neoplasms - genetics ; Breast Neoplasms - metabolism ; Breast Neoplasms - pathology ; Cancer ; Carbon ; Carcinoma ; Carcinoma, Ductal, Breast - genetics ; Carcinoma, Ductal, Breast - metabolism ; Carcinoma, Ductal, Breast - pathology ; Cardiology ; Cellular biology ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - metabolism ; DNA Methylation ; Enzyme-linked immunosorbent assay ; Epigenesis, Genetic ; Epigenetics ; Female ; Ferredoxin-NADP Reductase - genetics ; Ferredoxin-NADP Reductase - metabolism ; Gene Expression Regulation, Neoplastic ; Genotype & phenotype ; Glycine Hydroxymethyltransferase - genetics ; Glycine Hydroxymethyltransferase - metabolism ; Humans ; Life Sciences ; Medical Biochemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Metabolism ; Methylation ; Oncology ; Oxidative Stress ; Phenotype ; Physiological aspects ; Polymorphism, Genetic ; Prognosis ; Promoter Regions, Genetic ; Proteins ; Proto-Oncogene Proteins - genetics ; Proto-Oncogene Proteins - metabolism ; Sequence Analysis, DNA ; Sulfites ; Synergistic effect ; Transferases</subject><ispartof>Molecular and cellular biochemistry, 2012-02, Vol.361 (1-2), p.189-195</ispartof><rights>Springer Science+Business Media, LLC. 2011</rights><rights>COPYRIGHT 2012 Springer</rights><rights>Springer Science+Business Media, LLC. 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c610t-1a24f3717bed60a608e0912e960686b8054f035c216c400aed0d57e9a6cc97c13</citedby><cites>FETCH-LOGICAL-c610t-1a24f3717bed60a608e0912e960686b8054f035c216c400aed0d57e9a6cc97c13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21987236$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Naushad, Shaik Mohammad</creatorcontrib><creatorcontrib>Prayaga, Aruna</creatorcontrib><creatorcontrib>Digumarti, Raghunadha Rao</creatorcontrib><creatorcontrib>Gottumukkala, Suryanarayana Raju</creatorcontrib><creatorcontrib>Kutala, Vijay Kumar</creatorcontrib><title>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast</title><title>Molecular and cellular biochemistry</title><addtitle>Mol Cell Biochem</addtitle><addtitle>Mol Cell Biochem</addtitle><description>In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2′deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR–RFLP and PCR–AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08,
P
< 0.0001). COBRA analysis confirmed hypomethylation of BNIP3 promoter CpG island in these cases. CIMP phenotype of BNIP3 showed positive association with tubule formation (
P
= 0.034) and methionine synthase reductase (MTRR) A66G (
P
= 0.002); inverse association with cytosolic serine hydroxyl methyltransferase (cSHMT) C1420T (
P
< 0.005) and 8-oxodG (<10% vs. >10% methylation: 7.24 ± 2.77 ng/ml vs. 4.42 ± 2.93 ng/ml,
P
< 0.0005); and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (
P
< 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer.</description><subject>5-Methyltetrahydrofolate-homocysteine S-methyltransferase</subject><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Amplified Fragment Length Polymorphism Analysis</subject><subject>Analysis</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - metabolism</subject><subject>Breast Neoplasms - pathology</subject><subject>Cancer</subject><subject>Carbon</subject><subject>Carcinoma</subject><subject>Carcinoma, Ductal, Breast - genetics</subject><subject>Carcinoma, Ductal, Breast - metabolism</subject><subject>Carcinoma, Ductal, Breast - pathology</subject><subject>Cardiology</subject><subject>Cellular biology</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - metabolism</subject><subject>DNA Methylation</subject><subject>Enzyme-linked immunosorbent assay</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Ferredoxin-NADP Reductase - genetics</subject><subject>Ferredoxin-NADP Reductase - metabolism</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Genotype & phenotype</subject><subject>Glycine Hydroxymethyltransferase - genetics</subject><subject>Glycine Hydroxymethyltransferase - metabolism</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Medical Biochemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Metabolism</subject><subject>Methylation</subject><subject>Oncology</subject><subject>Oxidative Stress</subject><subject>Phenotype</subject><subject>Physiological aspects</subject><subject>Polymorphism, Genetic</subject><subject>Prognosis</subject><subject>Promoter Regions, Genetic</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>Sequence Analysis, DNA</subject><subject>Sulfites</subject><subject>Synergistic effect</subject><subject>Transferases</subject><issn>0300-8177</issn><issn>1573-4919</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><recordid>eNp9ksFu1DAQhiMEokvhAbggCw6UQ9oZOxvHx24pUKkCDnC2HGeyckmcrZ2s2D4NB56EJ8OrFBAIkA-27O__PTP6s-wxwjECyJOICAg5IObpJPKbO9kCl1LkhUJ1N1uAAMgrlPIgexDjFSQ4sfezA46qklyUi-zrynY5PzEN-WHrwhTZOa4Yqm9fPr00ufMjBWNH59dsE4aRnGeCHa3eXrwXLxh93gSK0Q2eucho49bkaXTWdN2OBVpPnRmpYfWODZ5ya0KdyJ5GUw-diz1LZs5vTXRbYs1kR2ap61jirPNDb9jQsjqQiePD7F5rukiPbvfD7OOr8w9nb_LLd68vzk4vc1sijDkaXrRCoqypKcGUUBEo5KRKKKuyrmBZtCCWlmNpCwBDDTRLScqU1ippURxmz2ff1Ov1RHHUvYv7ooynYYpaoQDBJYdEHv2XxEIozlXBi4Q-_QO9GqbgUx_Jj1cIstz__GyG1qYj7Xw7jGnue099KpaVUlVZVYk6_guVVkO9s2nIrUv3vwlwFtgwxBio1ZvgehN2GkHvI6TnCOkUC72PkL5Jmie39U51T81PxY_MJIDPQExPfk3hV0P_dv0OZnDQFQ</recordid><startdate>20120201</startdate><enddate>20120201</enddate><creator>Naushad, Shaik Mohammad</creator><creator>Prayaga, Aruna</creator><creator>Digumarti, Raghunadha Rao</creator><creator>Gottumukkala, Suryanarayana Raju</creator><creator>Kutala, Vijay Kumar</creator><general>Springer US</general><general>Springer</general><general>Springer Nature B.V</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>7QL</scope><scope>7QP</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20120201</creationdate><title>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast</title><author>Naushad, Shaik Mohammad ; Prayaga, Aruna ; Digumarti, Raghunadha Rao ; Gottumukkala, Suryanarayana Raju ; Kutala, Vijay Kumar</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c610t-1a24f3717bed60a608e0912e960686b8054f035c216c400aed0d57e9a6cc97c13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>5-Methyltetrahydrofolate-homocysteine S-methyltransferase</topic><topic>Adenovirus</topic><topic>Adenoviruses</topic><topic>Amplified Fragment Length Polymorphism Analysis</topic><topic>Analysis</topic><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Breast cancer</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - metabolism</topic><topic>Breast Neoplasms - pathology</topic><topic>Cancer</topic><topic>Carbon</topic><topic>Carcinoma</topic><topic>Carcinoma, Ductal, Breast - genetics</topic><topic>Carcinoma, Ductal, Breast - metabolism</topic><topic>Carcinoma, Ductal, Breast - pathology</topic><topic>Cardiology</topic><topic>Cellular biology</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - metabolism</topic><topic>DNA Methylation</topic><topic>Enzyme-linked immunosorbent assay</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Ferredoxin-NADP Reductase - genetics</topic><topic>Ferredoxin-NADP Reductase - metabolism</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genotype & phenotype</topic><topic>Glycine Hydroxymethyltransferase - genetics</topic><topic>Glycine Hydroxymethyltransferase - metabolism</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Medical Biochemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Metabolism</topic><topic>Methylation</topic><topic>Oncology</topic><topic>Oxidative Stress</topic><topic>Phenotype</topic><topic>Physiological aspects</topic><topic>Polymorphism, Genetic</topic><topic>Prognosis</topic><topic>Promoter Regions, Genetic</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>Sequence Analysis, DNA</topic><topic>Sulfites</topic><topic>Synergistic effect</topic><topic>Transferases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Naushad, Shaik Mohammad</creatorcontrib><creatorcontrib>Prayaga, Aruna</creatorcontrib><creatorcontrib>Digumarti, Raghunadha Rao</creatorcontrib><creatorcontrib>Gottumukkala, Suryanarayana Raju</creatorcontrib><creatorcontrib>Kutala, Vijay Kumar</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>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest 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>Science Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Technology Research Database</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)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>AUTh Library subscriptions: ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Science Journals</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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 Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Molecular and cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Naushad, Shaik Mohammad</au><au>Prayaga, Aruna</au><au>Digumarti, Raghunadha Rao</au><au>Gottumukkala, Suryanarayana Raju</au><au>Kutala, Vijay Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast</atitle><jtitle>Molecular and cellular biochemistry</jtitle><stitle>Mol Cell Biochem</stitle><addtitle>Mol Cell Biochem</addtitle><date>2012-02-01</date><risdate>2012</risdate><volume>361</volume><issue>1-2</issue><spage>189</spage><epage>195</epage><pages>189-195</pages><issn>0300-8177</issn><eissn>1573-4919</eissn><abstract>In view of recent studies highlighting the prognostic relevance of expression and CpG island methylator phenotype (CIMP) of Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) in invasive duct cell carcinoma (IDC), we hypothesized in this article that impaired one-carbon metabolism might influence CIMP phenotype of BNIP3. In order to substantiate the prognostic relevance of BNIP3, we explored its association with 8-oxo-2′deoxyguanosine (8-oxodG), a marker of oxidative stress with prognostic relevance. BNIP3 expression and CIMP phenotype were studied using semi-quantitative RT-PCR and combined bisulfite restriction analysis (COBRA), respectively, in 56 IDC tumors. Eight polymorphisms in one-carbon metabolism were studied using PCR–RFLP and PCR–AFLP approaches. 8-oxodG was measured using competitive ELISA kit. BNIP3 was found to be upregulated in IDC (cases vs. controls: 0.94 ± 0.05 vs. 0.18 ± 0.08,
P
< 0.0001). COBRA analysis confirmed hypomethylation of BNIP3 promoter CpG island in these cases. CIMP phenotype of BNIP3 showed positive association with tubule formation (
P
= 0.034) and methionine synthase reductase (MTRR) A66G (
P
= 0.002); inverse association with cytosolic serine hydroxyl methyltransferase (cSHMT) C1420T (
P
< 0.005) and 8-oxodG (<10% vs. >10% methylation: 7.24 ± 2.77 ng/ml vs. 4.42 ± 2.93 ng/ml,
P
< 0.0005); and no association with nuclear pleomorphism or mitotic index or ER, PR, and HER statuses. Synergistic effect of MTR A2756G and MTRR A66G variants on BNIP3 hypermethylator phenotype was clearly evident (
P
< 0.0007). MTRR A66G and cSHMT C1420T polymorphisms influence CIMP phenotype of BNIP3, thus epigenetically regulating BNIP3 in breast cancer. The linear association between BNIP3 and 8-oxodG substantiates the role of BNIP3 as redox sensor as well as prognostic marker in breast cancer.</abstract><cop>Boston</cop><pub>Springer US</pub><pmid>21987236</pmid><doi>10.1007/s11010-011-1103-z</doi><tpages>7</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0300-8177 |
| ispartof | Molecular and cellular biochemistry, 2012-02, Vol.361 (1-2), p.189-195 |
| issn | 0300-8177 1573-4919 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_913032720 |
| source | Springer Nature |
| subjects | 5-Methyltetrahydrofolate-homocysteine S-methyltransferase Adenovirus Adenoviruses Amplified Fragment Length Polymorphism Analysis Analysis Biochemistry Biomedical and Life Sciences Breast cancer Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer Carbon Carcinoma Carcinoma, Ductal, Breast - genetics Carcinoma, Ductal, Breast - metabolism Carcinoma, Ductal, Breast - pathology Cardiology Cellular biology Deoxyguanosine - analogs & derivatives Deoxyguanosine - metabolism DNA Methylation Enzyme-linked immunosorbent assay Epigenesis, Genetic Epigenetics Female Ferredoxin-NADP Reductase - genetics Ferredoxin-NADP Reductase - metabolism Gene Expression Regulation, Neoplastic Genotype & phenotype Glycine Hydroxymethyltransferase - genetics Glycine Hydroxymethyltransferase - metabolism Humans Life Sciences Medical Biochemistry Membrane Proteins - genetics Membrane Proteins - metabolism Metabolism Methylation Oncology Oxidative Stress Phenotype Physiological aspects Polymorphism, Genetic Prognosis Promoter Regions, Genetic Proteins Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Sequence Analysis, DNA Sulfites Synergistic effect Transferases |
| title | Bcl-2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3) expression is epigenetically regulated by one-carbon metabolism in invasive duct cell carcinoma of breast |
| url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-14T22%3A01%3A54IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Bcl-2/adenovirus%20E1B%2019%C2%A0kDa-interacting%20protein%203%20(BNIP3)%20expression%20is%20epigenetically%20regulated%20by%20one-carbon%20metabolism%20in%20invasive%20duct%20cell%20carcinoma%20of%20breast&rft.jtitle=Molecular%20and%20cellular%20biochemistry&rft.au=Naushad,%20Shaik%20Mohammad&rft.date=2012-02-01&rft.volume=361&rft.issue=1-2&rft.spage=189&rft.epage=195&rft.pages=189-195&rft.issn=0300-8177&rft.eissn=1573-4919&rft_id=info:doi/10.1007/s11010-011-1103-z&rft_dat=%3Cgale_proqu%3EA358998688%3C/gale_proqu%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c610t-1a24f3717bed60a608e0912e960686b8054f035c216c400aed0d57e9a6cc97c13%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=912810761&rft_id=info:pmid/21987236&rft_galeid=A358998688&rfr_iscdi=true |