Abstract
The Hedgehog pathway is molecularly linked to increased resistance to cisplatin and increased repair of platinum-DNA damage, through C-JUN. GLI1, which has five known isoforms, is a positive transcriptional regulator in Hedgehog. Southwestern blot assay, EMSA and ChIP assays indicate that only one of five isoforms of GLI1 may be responsible for the Hedgehog link with C-JUN and thus, increased platinum-DNA adduct repair. Cancer tissues express this 130-kDa isoform at levels 6-fold higher than non-malignant tissues; and this isoform exists in abundance in six of seven ovarian cancer cell lines examined.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Cisplatin / therapeutic use
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DNA Damage / drug effects
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Drug Resistance, Neoplasm / genetics*
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Female
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Hedgehog Proteins / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases / genetics*
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Ovarian Neoplasms / drug therapy
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Ovarian Neoplasms / genetics*
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Transcription Factors / genetics*
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Transcription Factors / metabolism
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Tumor Cells, Cultured
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Zinc Finger Protein GLI1
Substances
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GLI1 protein, human
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Hedgehog Proteins
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Protein Isoforms
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Transcription Factors
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Zinc Finger Protein GLI1
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JNK Mitogen-Activated Protein Kinases
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Cisplatin