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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2007-11-20
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pubmed:abstractText |
BCL-2 is the prototypic anti-apoptotic protein involved in the regulation of apoptosis. Overexpression of BCL-2 is common in pancreatic cancer and confers resistance to the apoptotic effect of chemo- and radiotherapy. Although these cellular effects of BCL-2 are traditionally related to pathways involving the mitochondrial membrane, we sought to investigate whether BCL-2 is involved in other signaling pathways regulating cell survival and focused on AKT. We examined the effect of overexpression of BCL-2 in the MIA-PaCa-2 human pancreatic cancer cell line on the function and subcellular location of AKT. We observed that the stable subclones of MIA-PaCa-2 overexpressing BCL-2 demonstrated increased activity of AKT as well as IKK (a downstream target of AKT), increasing the transcriptional activity of NF-kappaB. Using immunoprecipitation techniques, we observed co-immunoprecipitation of AKT and BCL-2. Immunocytochemistry demonstrated co-localization of BCL-2 and AKT, which was abrogated by treatment with HA14-1, a small molecule inhibitor of BH-3-mediated protein interaction by BCL-2. Furthermore, treatment with HA14-1 decreased phosphorylation of AKT and increased sensitivity to the apoptotic effect of the chemotherapeutic agent, paclitaxel. These results demonstrate an additional mechanism of regulation of cell survival mediated by BCL-2, namely through AKT activation, in the MIA-PaCa-2 pancreatic cancer cell line. Therefore, directed inhibition of BCL-2 may alter diverse pathways controlling cell survival and overcome the apoptotic resistance that is the hallmark of pancreatic cancer.
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pubmed:grant |
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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/AKT1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, Phytogenic,
http://linkedlifedata.com/resource/pubmed/chemical/Benzopyrans,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases, Renilla,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/Paclitaxel,
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/ethyl...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0730-2312
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pubmed:author |
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pubmed:copyrightInfo |
(c) 2007 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1171-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:17960583-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:17960583-Apoptosis,
pubmed-meshheading:17960583-Benzopyrans,
pubmed-meshheading:17960583-Cell Line, Tumor,
pubmed-meshheading:17960583-Cell Survival,
pubmed-meshheading:17960583-Clone Cells,
pubmed-meshheading:17960583-DNA, Complementary,
pubmed-meshheading:17960583-Enzyme Activation,
pubmed-meshheading:17960583-Enzyme Inhibitors,
pubmed-meshheading:17960583-Genes, Reporter,
pubmed-meshheading:17960583-Humans,
pubmed-meshheading:17960583-Immunohistochemistry,
pubmed-meshheading:17960583-Luciferases, Renilla,
pubmed-meshheading:17960583-NF-kappa B,
pubmed-meshheading:17960583-Nitriles,
pubmed-meshheading:17960583-Paclitaxel,
pubmed-meshheading:17960583-Pancreatic Neoplasms,
pubmed-meshheading:17960583-Phosphorylation,
pubmed-meshheading:17960583-Precipitin Tests,
pubmed-meshheading:17960583-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:17960583-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:17960583-Signal Transduction,
pubmed-meshheading:17960583-Subcellular Fractions,
pubmed-meshheading:17960583-Transfection
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pubmed:year |
2007
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pubmed:articleTitle |
BCL-2 functions as an activator of the AKT signaling pathway in pancreatic cancer.
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pubmed:affiliation |
Department of Surgery, University of California Davis School of Medicine, Sacramento, California, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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