Abstract
Telomerase activity is present in >90% of all tumors and appears to be regulated by the phosphatidylinositol 3-kinase signaling pathway. Here we demonstrate that Akt is not involved in the signaling cascade for telomerase regulation in ovarian surface epithelial cells. However, we showed that c-Jun NH2-kinase induces telomerase activity, that inhibition of JNK by JIP abrogates telomerase activity, and that JNK expression activates transcription of a reporter gene fused to the hTERT promoter sequence. Consequently, our data show that JNK is a key regulator of telomerase activity and, hence, may provide new perspectives on tumorigenesis that could be exploited for novel therapeutic strategies.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Anisomycin / pharmacology
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DNA-Binding Proteins
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Enzyme Induction / drug effects
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Epithelial Cells / enzymology
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Female
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Gene Expression Regulation, Enzymologic
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Gene Expression Regulation, Neoplastic
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Humans
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases / genetics
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Mitogen-Activated Protein Kinases / metabolism*
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Ovarian Neoplasms / enzymology*
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Ovarian Neoplasms / genetics
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Phosphatidylinositol 3-Kinases / metabolism
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-akt
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Telomerase / biosynthesis
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Telomerase / genetics
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Telomerase / metabolism*
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Transcription, Genetic
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Transcriptional Activation
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Transfection
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Tumor Cells, Cultured
Substances
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DNA-Binding Proteins
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Proto-Oncogene Proteins
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RNA, Messenger
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Anisomycin
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AKT1 protein, human
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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Telomerase