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rdf:type |
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lifeskim:mentions |
umls-concept:C0017262,
umls-concept:C0040106,
umls-concept:C0162638,
umls-concept:C0185117,
umls-concept:C0332325,
umls-concept:C0664336,
umls-concept:C0699790,
umls-concept:C1412452,
umls-concept:C1444748,
umls-concept:C1514559,
umls-concept:C1518174,
umls-concept:C1519554,
umls-concept:C1539477,
umls-concept:C1540126,
umls-concept:C2911684
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pubmed:issue |
5
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pubmed:dateCreated |
2006-4-24
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pubmed:abstractText |
The present work was conducted to further examine the effects of thymosin beta-4 (Tbeta4) upregulation on the apoptosis of SW480 colon cancer cells induced by T cells and various chemotherapeutic agents because reduced susceptibility to the cytotoxicity of an anti-Fas IgM (CH-11) in Tbeta4-overexpressing cells has previously been reported by us. As expected, Tbeta4 overexpressers were also more resistant to the killing effect of FasL-bearing Jurkat T cells. On the other hand, pretreating these cells with an MMP inhibitor restored not only their Fas levels but also their sensitivity to CH-11, suggesting a pivotal role of MMP in downregulating Fas in Tbeta4 overexpressers. Interestingly, while the susceptibilities of Tbeta4 overexpressers to 5-FU and irinotecan remained unchanged, they were more resistant to doxorubicin and etoposide which triggered apoptosis via a mitochondrial pathway. Concordantly, activation of both caspases 9 and 3 in Tbeta4 overexpressers by the two aforementioned topoisomerase II inhibitors was dramatically abrogated which could be accounted mainly by an increased expression of Survivin, a critical anti-apoptotic factor. Finally, poor survival was found in stage III colon cancer patients whose tumors were stained positively by the anti-Survivin antibody. Thus, advantages such as immune evasion and resistance to anticancer drug-induced apoptosis acquired by colon cancer cells through Tbeta4 overexpression might facilitate their survival during metastasis and chemotherapy.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD95,
http://linkedlifedata.com/resource/pubmed/chemical/BIRC5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Caspases,
http://linkedlifedata.com/resource/pubmed/chemical/FASLG protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Fas Ligand Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Inhibitor of Apoptosis Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Thymosin,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase II Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factors,
http://linkedlifedata.com/resource/pubmed/chemical/thymosin beta(4)
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0143-3334
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
27
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
936-44
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16364925-Antigens, CD95,
pubmed-meshheading:16364925-Apoptosis,
pubmed-meshheading:16364925-Caspases,
pubmed-meshheading:16364925-Cell Line, Tumor,
pubmed-meshheading:16364925-Cell Survival,
pubmed-meshheading:16364925-Enzyme Activation,
pubmed-meshheading:16364925-Fas Ligand Protein,
pubmed-meshheading:16364925-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:16364925-Humans,
pubmed-meshheading:16364925-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:16364925-Inhibitory Concentration 50,
pubmed-meshheading:16364925-Membrane Glycoproteins,
pubmed-meshheading:16364925-Microtubule-Associated Proteins,
pubmed-meshheading:16364925-Neoplasm Proteins,
pubmed-meshheading:16364925-Prognosis,
pubmed-meshheading:16364925-Thymosin,
pubmed-meshheading:16364925-Time Factors,
pubmed-meshheading:16364925-Topoisomerase II Inhibitors,
pubmed-meshheading:16364925-Tumor Necrosis Factors
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pubmed:year |
2006
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pubmed:articleTitle |
Overexpression of thymosin beta-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via downregulating Fas and upregulating Survivin expression, respectively.
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pubmed:affiliation |
Institute of Pharmacology, College of Medicine, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan, R.O. China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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