title: GLI1 upregulates C-JUN through a specific 130-kDa isoform.
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.
authors.affiliation: National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Amable
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Elaine
authors.initials: E
authors.lastname: Gavin
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kudo
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Erhong
authors.initials: E
authors.lastname: Meng
authors.affiliation: Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA.
authors.forename: Rodney P
authors.initials: RP
authors.lastname: Rocconi
authors.affiliation: Department of Pathology, Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
authors.forename: Lalita A
authors.initials: LA
authors.lastname: Shevde
authors.affiliation: National Institute on Minority Health and Health Disparities, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Eddie
authors.initials: E
authors.lastname: Reed
mesh_terms: D002945:Cisplatin / Q000627:therapeutic use; D004249:DNA Damage / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D053823:Hedgehog Proteins / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D053823:Hedgehog Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin