Transcriptional and post-translational regulation of Bim is essential for TGF-β and TNF-α-induced apoptosis of gastric cancer cell
DC Field | Value | Language |
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dc.contributor.author | Ha Thi, H.T. | - |
dc.contributor.author | Lim, H.-S. | - |
dc.contributor.author | Kim, J. | - |
dc.contributor.author | Kim, Y.-M. | - |
dc.contributor.author | Kim, H.-Y. | - |
dc.contributor.author | Hong, S. | - |
dc.date.available | 2020-02-29T00:47:52Z | - |
dc.date.created | 2020-02-12 | - |
dc.date.issued | 2013-06 | - |
dc.identifier.issn | 0304-4165 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/14920 | - |
dc.description.abstract | Background Tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) are well known as central signaling molecules in natural antitumor mechanisms. However, some cancer cells are resistant to TNF-α or TGF-β-induced death signaling. Herein, we investigated synergistic activities of TGF-β and TNF-α and molecular mechanisms involved in apoptosis of gastric cancer cells. Methods SNU620, a human gastric carcinoma cell line was tested for cell viability by treatment of TGF-β in combination with TNF-α. Cell apoptosis, proliferation, caspase activation and gene expression were tested using flow cytometry, Western blot, MTT assay, luciferase assay and real-time qRT-PCR analysis. Knockdown of target genes were performed using lentiviral shRNA system. Results TGF-β sensitizes SNU620 cells undergoing TNF-α-induced caspase-dependent apoptosis. TNF-α and TGF-β synergistically induced the degradation of poly(ADP-ribose) polymerase (PARP) and caspase cascade activation. We also confirmed that c-Jun NH2-terminal kinase (JNK) and Smad3 play critical roles in the apoptotic pathway. In addition, a pro-apoptotic protein Bim was critical for apoptosis and was regulated by TGF-β and TNF-α at the transcriptional and post-translational levels. Expression of Bim was induced at the transcriptional level by Smad3 while Bim protein stability was maintained by a JNK-mediated pathway. Conclusion By understanding the synergistic activation of TGF-β and TNF-α in apoptosis, we may have a chance to identify good therapeutic approaches for the treatment of cancers that are resistant to death signals. General significance Our results indicate that TGF-β and TNF-α act in concert to activate apoptosis in gastric cancer cell through crosstalk between Smad and JNK signaling pathways. © 2013 Elsevier B.V. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE BV | - |
dc.relation.isPartOf | Biochimica et Biophysica Acta - General Subjects | - |
dc.title | Transcriptional and post-translational regulation of Bim is essential for TGF-β and TNF-α-induced apoptosis of gastric cancer cell | - |
dc.type | Article | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.identifier.wosid | 000319232400028 | - |
dc.identifier.doi | 10.1016/j.bbagen.2013.03.006 | - |
dc.identifier.bibliographicCitation | Biochimica et Biophysica Acta - General Subjects, v.1830, no.6, pp.3584 - 3592 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-84875970281 | - |
dc.citation.endPage | 3592 | - |
dc.citation.startPage | 3584 | - |
dc.citation.title | Biochimica et Biophysica Acta - General Subjects | - |
dc.citation.volume | 1830 | - |
dc.citation.number | 6 | - |
dc.contributor.affiliatedAuthor | Ha Thi, H.T. | - |
dc.contributor.affiliatedAuthor | Lim, H.-S. | - |
dc.contributor.affiliatedAuthor | Kim, J. | - |
dc.contributor.affiliatedAuthor | Kim, Y.-M. | - |
dc.contributor.affiliatedAuthor | Kim, H.-Y. | - |
dc.contributor.affiliatedAuthor | Hong, S. | - |
dc.type.docType | Article | - |
dc.subject.keywordAuthor | Bim Apoptosis | - |
dc.subject.keywordAuthor | c-Jun | - |
dc.subject.keywordAuthor | NH2-terminal kinase | - |
dc.subject.keywordAuthor | Smad3 | - |
dc.subject.keywordAuthor | Transforming growth factor-β | - |
dc.subject.keywordAuthor | Tumor necrosis factor-α | - |
dc.subject.keywordPlus | 3 (4,5 dimethyl 2 thiazolyl) 2,5 diphenyltetrazolium bromide | - |
dc.subject.keywordPlus | BIM protein | - |
dc.subject.keywordPlus | caspase 3 | - |
dc.subject.keywordPlus | caspase 8 | - |
dc.subject.keywordPlus | luciferase | - |
dc.subject.keywordPlus | nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase | - |
dc.subject.keywordPlus | short hairpin RNA | - |
dc.subject.keywordPlus | Smad2 protein | - |
dc.subject.keywordPlus | Smad3 protein | - |
dc.subject.keywordPlus | stress activated protein kinase | - |
dc.subject.keywordPlus | transforming growth factor beta | - |
dc.subject.keywordPlus | tumor necrosis factor alpha | - |
dc.subject.keywordPlus | apoptosis | - |
dc.subject.keywordPlus | article | - |
dc.subject.keywordPlus | cancer cell culture | - |
dc.subject.keywordPlus | cell proliferation | - |
dc.subject.keywordPlus | cell viability | - |
dc.subject.keywordPlus | controlled study | - |
dc.subject.keywordPlus | enzyme activation | - |
dc.subject.keywordPlus | enzyme degradation | - |
dc.subject.keywordPlus | flow cytometry | - |
dc.subject.keywordPlus | gene expression regulation | - |
dc.subject.keywordPlus | gene silencing | - |
dc.subject.keywordPlus | gene targeting | - |
dc.subject.keywordPlus | human | - |
dc.subject.keywordPlus | human cell | - |
dc.subject.keywordPlus | molecular dynamics | - |
dc.subject.keywordPlus | priority journal | - |
dc.subject.keywordPlus | protein expression | - |
dc.subject.keywordPlus | protein function | - |
dc.subject.keywordPlus | protein processing | - |
dc.subject.keywordPlus | protein stability | - |
dc.subject.keywordPlus | quantitative analysis | - |
dc.subject.keywordPlus | reverse transcription polymerase chain reaction | - |
dc.subject.keywordPlus | signal transduction | - |
dc.subject.keywordPlus | stomach cancer | - |
dc.subject.keywordPlus | transcription regulation | - |
dc.subject.keywordPlus | Western blotting | - |
dc.subject.keywordPlus | Apoptosis | - |
dc.subject.keywordPlus | Apoptosis Regulatory Proteins | - |
dc.subject.keywordPlus | Caspases | - |
dc.subject.keywordPlus | Cell Line, Tumor | - |
dc.subject.keywordPlus | Female | - |
dc.subject.keywordPlus | Gene Expression Regulation, Neoplastic | - |
dc.subject.keywordPlus | Humans | - |
dc.subject.keywordPlus | JNK Mitogen-Activated Protein Kinases | - |
dc.subject.keywordPlus | Male | - |
dc.subject.keywordPlus | MAP Kinase Signaling System | - |
dc.subject.keywordPlus | Membrane Proteins | - |
dc.subject.keywordPlus | Protein Stability | - |
dc.subject.keywordPlus | Proto-Oncogene Proteins | - |
dc.subject.keywordPlus | Smad3 Protein | - |
dc.subject.keywordPlus | Stomach Neoplasms | - |
dc.subject.keywordPlus | Transcription, Genetic | - |
dc.subject.keywordPlus | Transforming Growth Factor beta | - |
dc.subject.keywordPlus | Tumor Necrosis Factor-alpha | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
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