The FOXM1-induced resistance to oxaliplatin is partially mediated by its novel target gene Mcl-1 in gastric cancer cells.
Identifieur interne : 000285 ( Main/Exploration ); précédent : 000284; suivant : 000286The FOXM1-induced resistance to oxaliplatin is partially mediated by its novel target gene Mcl-1 in gastric cancer cells.
Auteurs : Chang-Jiang Hu [République populaire de Chine] ; Bin Wang [République populaire de Chine] ; Bo Tang [République populaire de Chine] ; Bai-Jun Chen [République populaire de Chine] ; Yu-Feng Xiao [République populaire de Chine] ; Yong Qin [République populaire de Chine] ; Xin Yong [République populaire de Chine] ; Gang Luo [République populaire de Chine] ; Jian-Wei Zhang [République populaire de Chine] ; Dan Zhang [République populaire de Chine] ; Song Li [États-Unis] ; Fengtian He [République populaire de Chine] ; Shi-Ming Yang [République populaire de Chine]Source :
- Biochimica et biophysica acta [ 0006-3002 ] ; 2015.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen, Apoptose (), Composés organiques du platine (administration et posologie), Facteurs de transcription Forkhead (biosynthèse), Facteurs de transcription Forkhead (génétique), Femelle, Humains, Mâle, Prolifération cellulaire (), Pronostic, Protéine M1 à motif en tête de fourche, Protéine Mcl-1 (biosynthèse), Protéine Mcl-1 (génétique), Régions promotrices (génétique), Régulation de l'expression des gènes tumoraux (), Résistance aux médicaments antinéoplasiques (génétique), Sujet âgé, Tumeurs de l'estomac (anatomopathologie), Tumeurs de l'estomac (génétique), Tumeurs de l'estomac (traitement médicamenteux).
- MESH :
- administration et posologie : Composés organiques du platine.
- anatomopathologie : Tumeurs de l'estomac.
- biosynthèse : Facteurs de transcription Forkhead, Protéine Mcl-1.
- génétique : Facteurs de transcription Forkhead, Protéine Mcl-1, Résistance aux médicaments antinéoplasiques, Tumeurs de l'estomac.
- traitement médicamenteux : Tumeurs de l'estomac.
- Adulte d'âge moyen, Apoptose, Femelle, Humains, Mâle, Prolifération cellulaire, Pronostic, Protéine M1 à motif en tête de fourche, Régions promotrices (génétique), Régulation de l'expression des gènes tumoraux, Sujet âgé.
English descriptors
- KwdEn :
- Aged, Apoptosis (drug effects), Cell Proliferation (drug effects), Drug Resistance, Neoplasm (genetics), Female, Forkhead Box Protein M1, Forkhead Transcription Factors (biosynthesis), Forkhead Transcription Factors (genetics), Gene Expression Regulation, Neoplastic (drug effects), Humans, Male, Middle Aged, Myeloid Cell Leukemia Sequence 1 Protein (biosynthesis), Myeloid Cell Leukemia Sequence 1 Protein (genetics), Organoplatinum Compounds (administration & dosage), Prognosis, Promoter Regions, Genetic, Stomach Neoplasms (drug therapy), Stomach Neoplasms (genetics), Stomach Neoplasms (pathology).
- MESH :
- chemical , administration & dosage : Organoplatinum Compounds.
- chemical , biosynthesis : Forkhead Transcription Factors, Myeloid Cell Leukemia Sequence 1 Protein.
- chemical , genetics : Forkhead Transcription Factors, Myeloid Cell Leukemia Sequence 1 Protein.
- chemical : Forkhead Box Protein M1.
- drug effects : Apoptosis, Cell Proliferation, Gene Expression Regulation, Neoplastic.
- drug therapy : Stomach Neoplasms.
- genetics : Drug Resistance, Neoplasm, Stomach Neoplasms.
- pathology : Stomach Neoplasms.
- Aged, Female, Humans, Male, Middle Aged, Prognosis, Promoter Regions, Genetic.
Abstract
Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that belongs to the Bcl-2 family. The aberrant expression of Mcl-1 is important for sensitivity to chemotherapy drugs in gastric cancer. However, the regulatory mechanism of Mcl-1 in gastric cancer cells remains unclear. In this study, we first found that Forkhead box M1 (FOXM1) and Mcl-1 expression levels were positively correlated in human gastric cancer specimens and that both are associated with poor prognosis of patients treated with oxaliplatin. Second, we demonstrated that the expression level of Mcl-1 was correlated with FOXM1 expression in gastric cancer cells. Third, reporter assays showed that FOXM1 upregulated the promoter activity of the Mcl-1 gene. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays further demonstrated that FOXM1 could bind to a particular site (-635acaaacaa-628) in the promoter region of the Mcl-1 gene. Moreover, CCK-8 assays and analyses of apoptosis revealed that the suppression of the FOXM1/Mcl-1 pathway induced apoptosis and thus increased sensitivity to oxaliplatin in gastric cancer cells, whereas the enhancement of the FOXM1/Mcl-1 pathway inhibited apoptosis and decreased sensitivity to oxaliplatin in gastric cancer cells. Taken together, this study is the first to not only show that Mcl-1 is a novel target gene of FOXM1 but also suggest that targeting FOXM1/Mcl-1 may be a novel strategy to enhance sensitivity to oxaliplatin in gastric cancer.
DOI: 10.1016/j.bbagrm.2014.11.008
PubMed: 25482013
Affiliations:
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Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Wang, Bin" sort="Wang, Bin" uniqKey="Wang B" first="Bin" last="Wang">Bin Wang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038</wicri:regionArea><wicri:noRegion>Chongqing 400038</wicri:noRegion></affiliation></author><author><name sortKey="Tang, Bo" sort="Tang, Bo" uniqKey="Tang B" first="Bo" last="Tang">Bo Tang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Chen, Bai Jun" sort="Chen, Bai Jun" uniqKey="Chen B" first="Bai-Jun" last="Chen">Bai-Jun Chen</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Xiao, Yu Feng" sort="Xiao, Yu Feng" uniqKey="Xiao Y" first="Yu-Feng" last="Xiao">Yu-Feng Xiao</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Qin, Yong" sort="Qin, Yong" uniqKey="Qin Y" first="Yong" last="Qin">Yong Qin</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Yong, Xin" sort="Yong, Xin" uniqKey="Yong X" first="Xin" last="Yong">Xin Yong</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Luo, Gang" sort="Luo, Gang" uniqKey="Luo G" first="Gang" last="Luo">Gang Luo</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Jian Wei" sort="Zhang, Jian Wei" uniqKey="Zhang J" first="Jian-Wei" last="Zhang">Jian-Wei Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Dan" sort="Zhang, Dan" uniqKey="Zhang D" first="Dan" last="Zhang">Dan Zhang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author><author><name sortKey="Li, Song" sort="Li, Song" uniqKey="Li S" first="Song" last="Li">Song Li</name><affiliation wicri:level="4"><nlm:affiliation>Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, United States.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="He, Fengtian" sort="He, Fengtian" uniqKey="He F" first="Fengtian" last="He">Fengtian He</name><affiliation wicri:level="1"><nlm:affiliation>Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: hefengtian06@aliyun.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038</wicri:regionArea><wicri:noRegion>Chongqing 400038</wicri:noRegion></affiliation></author><author><name sortKey="Yang, Shi Ming" sort="Yang, Shi Ming" uniqKey="Yang S" first="Shi-Ming" last="Yang">Shi-Ming Yang</name><affiliation wicri:level="1"><nlm:affiliation>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: shimingyang@yahoo.com.</nlm:affiliation><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037</wicri:regionArea><wicri:noRegion>Chongqing 400037</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biochimica et biophysica acta</title><idno type="ISSN">0006-3002</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Apoptosis (drug effects)</term><term>Cell Proliferation (drug effects)</term><term>Drug Resistance, Neoplasm (genetics)</term><term>Female</term><term>Forkhead Box Protein M1</term><term>Forkhead Transcription Factors (biosynthesis)</term><term>Forkhead Transcription Factors (genetics)</term><term>Gene Expression Regulation, Neoplastic (drug effects)</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Myeloid Cell Leukemia Sequence 1 Protein (biosynthesis)</term><term>Myeloid Cell Leukemia Sequence 1 Protein (genetics)</term><term>Organoplatinum Compounds (administration & dosage)</term><term>Prognosis</term><term>Promoter Regions, Genetic</term><term>Stomach Neoplasms (drug therapy)</term><term>Stomach Neoplasms (genetics)</term><term>Stomach Neoplasms (pathology)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Apoptose ()</term><term>Composés organiques du platine (administration et posologie)</term><term>Facteurs de transcription Forkhead (biosynthèse)</term><term>Facteurs de transcription Forkhead (génétique)</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Prolifération cellulaire ()</term><term>Pronostic</term><term>Protéine M1 à motif en tête de fourche</term><term>Protéine Mcl-1 (biosynthèse)</term><term>Protéine Mcl-1 (génétique)</term><term>Régions promotrices (génétique)</term><term>Régulation de l'expression des gènes tumoraux ()</term><term>Résistance aux médicaments antinéoplasiques (génétique)</term><term>Sujet âgé</term><term>Tumeurs de l'estomac (anatomopathologie)</term><term>Tumeurs de l'estomac (génétique)</term><term>Tumeurs de l'estomac (traitement médicamenteux)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Organoplatinum Compounds</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Forkhead Transcription Factors</term><term>Myeloid Cell Leukemia Sequence 1 Protein</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Forkhead Transcription Factors</term><term>Myeloid Cell Leukemia Sequence 1 Protein</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Forkhead Box Protein M1</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Composés organiques du platine</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Tumeurs de l'estomac</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Facteurs de transcription Forkhead</term><term>Protéine Mcl-1</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Cell Proliferation</term><term>Gene Expression Regulation, Neoplastic</term></keywords><keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Stomach Neoplasms</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Drug Resistance, Neoplasm</term><term>Stomach Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Facteurs de transcription Forkhead</term><term>Protéine Mcl-1</term><term>Résistance aux médicaments antinéoplasiques</term><term>Tumeurs de l'estomac</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Stomach Neoplasms</term></keywords><keywords scheme="MESH" qualifier="traitement médicamenteux" xml:lang="fr"><term>Tumeurs de l'estomac</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Female</term><term>Humans</term><term>Male</term><term>Middle Aged</term><term>Prognosis</term><term>Promoter Regions, Genetic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term><term>Apoptose</term><term>Femelle</term><term>Humains</term><term>Mâle</term><term>Prolifération cellulaire</term><term>Pronostic</term><term>Protéine M1 à motif en tête de fourche</term><term>Régions promotrices (génétique)</term><term>Régulation de l'expression des gènes tumoraux</term><term>Sujet âgé</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic protein that belongs to the Bcl-2 family. The aberrant expression of Mcl-1 is important for sensitivity to chemotherapy drugs in gastric cancer. However, the regulatory mechanism of Mcl-1 in gastric cancer cells remains unclear. In this study, we first found that Forkhead box M1 (FOXM1) and Mcl-1 expression levels were positively correlated in human gastric cancer specimens and that both are associated with poor prognosis of patients treated with oxaliplatin. Second, we demonstrated that the expression level of Mcl-1 was correlated with FOXM1 expression in gastric cancer cells. Third, reporter assays showed that FOXM1 upregulated the promoter activity of the Mcl-1 gene. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation (ChIP) assays further demonstrated that FOXM1 could bind to a particular site (-635acaaacaa-628) in the promoter region of the Mcl-1 gene. Moreover, CCK-8 assays and analyses of apoptosis revealed that the suppression of the FOXM1/Mcl-1 pathway induced apoptosis and thus increased sensitivity to oxaliplatin in gastric cancer cells, whereas the enhancement of the FOXM1/Mcl-1 pathway inhibited apoptosis and decreased sensitivity to oxaliplatin in gastric cancer cells. Taken together, this study is the first to not only show that Mcl-1 is a novel target gene of FOXM1 but also suggest that targeting FOXM1/Mcl-1 may be a novel strategy to enhance sensitivity to oxaliplatin in gastric cancer.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Hu, Chang Jiang" sort="Hu, Chang Jiang" uniqKey="Hu C" first="Chang-Jiang" last="Hu">Chang-Jiang Hu</name></noRegion><name sortKey="Chen, Bai Jun" sort="Chen, Bai Jun" uniqKey="Chen B" first="Bai-Jun" last="Chen">Bai-Jun Chen</name><name sortKey="He, Fengtian" sort="He, Fengtian" uniqKey="He F" first="Fengtian" last="He">Fengtian He</name><name sortKey="Luo, Gang" sort="Luo, Gang" uniqKey="Luo G" first="Gang" last="Luo">Gang Luo</name><name sortKey="Qin, Yong" sort="Qin, Yong" uniqKey="Qin Y" first="Yong" last="Qin">Yong Qin</name><name sortKey="Tang, Bo" sort="Tang, Bo" uniqKey="Tang B" first="Bo" last="Tang">Bo Tang</name><name sortKey="Wang, Bin" sort="Wang, Bin" uniqKey="Wang B" first="Bin" last="Wang">Bin Wang</name><name sortKey="Xiao, Yu Feng" sort="Xiao, Yu Feng" uniqKey="Xiao Y" first="Yu-Feng" last="Xiao">Yu-Feng Xiao</name><name sortKey="Yang, Shi Ming" sort="Yang, Shi Ming" uniqKey="Yang S" first="Shi-Ming" last="Yang">Shi-Ming Yang</name><name sortKey="Yong, Xin" sort="Yong, Xin" uniqKey="Yong X" first="Xin" last="Yong">Xin Yong</name><name sortKey="Zhang, Dan" sort="Zhang, Dan" uniqKey="Zhang D" first="Dan" last="Zhang">Dan Zhang</name><name sortKey="Zhang, Jian Wei" sort="Zhang, Jian Wei" uniqKey="Zhang J" first="Jian-Wei" last="Zhang">Jian-Wei Zhang</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Li, Song" sort="Li, Song" uniqKey="Li S" first="Song" last="Li">Song Li</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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