Source:http://linkedlifedata.com/resource/pubmed/id/11593385
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
41
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| pubmed:dateCreated |
2001-10-10
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| pubmed:abstractText |
Interleukin-6 (IL-6), a multifunctional cytokine, has recently been implicated in human cervical cancer, though the mechanism remains elusive. This study demonstrates that the anti-apoptotic protein Mcl-1 and IL-6 was concomitantly expressed in human cervical cancer tissues and cell lines, but not in normal cervix tissues. Upon IL-6 treatment, Mcl-1, but not other Bcl-2 family members, was rapidly up-regulated peaking at 4-8 h in human cervical cancer C33A cells. Supporting this observation, using anti-IL-6 or anti-IL-6 receptor antibody to interrupt the IL-6 autocrine loop in SiHa cells significantly reduced cellular level of Mcl-1. This study hypothesizes that the expression of Mcl-1 in cervical cancer cells is regulated by IL-6. The matter of which signaling pathways transduced by IL-6 is responsible for the Mcl-1 up-regulation is further investigated herein. Blocking the STAT3 or MAPK pathway with dominant-negative mutant STAT3F or the MEK inhibitor PD98059 failed to inhibit IL-6-mediated Mcl-1 expression. Meanwhile, the IL-6-induced Mcl-1 up-regulation was effectively abolished by treatment with PI 3-K inhibitors, LY294002. Additionally, overexpression of dominant-negative (dn) Akt in C33A cells could inhibit the IL-6-induced increase of Mcl-1. Finally, overexpression of IL-6 in C33A cells caused a markable resistance to apoptosis induced by doxorubicin or cisplatin. Transient transfection of IL-6-overexpressed cells with a mcl-1 antisense vector, leading to the attenuation of their apoptosis-resistant activity. In conclusion, the data herein suggest that IL-6 regulated the mcl-1 expression via a PI 3-K/Akt-dependent pathway that may facilitate the oncogenesis of human cervical cancer by modulating the apoptosis threshold.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Green Fluorescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-6,
http://linkedlifedata.com/resource/pubmed/chemical/Luminescent Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Neoplasm Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/myeloid cell leukemia sequence 1...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0950-9232
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
13
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| pubmed:volume |
20
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
5799-809
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:11593385-Antineoplastic Agents,
pubmed-meshheading:11593385-Apoptosis,
pubmed-meshheading:11593385-Carcinoma, Squamous Cell,
pubmed-meshheading:11593385-Doxorubicin,
pubmed-meshheading:11593385-Female,
pubmed-meshheading:11593385-Green Fluorescent Proteins,
pubmed-meshheading:11593385-HeLa Cells,
pubmed-meshheading:11593385-Humans,
pubmed-meshheading:11593385-Interleukin-6,
pubmed-meshheading:11593385-Luminescent Proteins,
pubmed-meshheading:11593385-Neoplasm Proteins,
pubmed-meshheading:11593385-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11593385-Proto-Oncogene Proteins,
pubmed-meshheading:11593385-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:11593385-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:11593385-Signal Transduction,
pubmed-meshheading:11593385-Transfection,
pubmed-meshheading:11593385-Tumor Cells, Cultured,
pubmed-meshheading:11593385-Up-Regulation,
pubmed-meshheading:11593385-Uterine Cervical Neoplasms
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| pubmed:year |
2001
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| pubmed:articleTitle |
The anti-apoptotic role of interleukin-6 in human cervical cancer is mediated by up-regulation of Mcl-1 through a PI 3-K/Akt pathway.
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| pubmed:affiliation |
Department of Obstetrics and Gynecology, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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