title: CtBP1 is expressed in melanoma and represses the transcription of p16INK4a and Brca1.
abstract: Carboxyl-terminal binding protein 1 (CtBP1) has been shown to suppress the transcription of several tumor suppressors in vitro. Paradoxically, a previous report showed that CtBP1 mRNA was downregulated in melanoma. Using immunostaining, we found that a large percentage of human melanomas were positive for CtBP1 protein. Furthermore, we demonstrated that CtBP1 expression in melanoma cells contributes to cell proliferation and genome instability, two aspects promoting melanoma initiation and progression. Breast cancer susceptibility gene 1 (Brca1), a core protein in DNA-damage repair, was repressed by CtBP1 in melanoma cells. Consistently, Brca1 loss in human malignant melanoma tissues was found to be inversely correlated with CtBP1 expression levels. In addition, the inhibitor of cyclin-dependent protein kinases (CDKs), p16INK4a, whose loss has been related to the pathogenesis of melanoma, was repressed by CtBP1 as well. Our findings suggest an important role of CtBP1 in the transcriptional control of p16INK4a and Brca1, with CtBP1 overexpression potentially contributing to increased proliferation and DNA damage in melanoma.
authors.affiliation: Department of Dermatology, University of Colorado, Denver, Aurora, Colorado 80045, USA.
authors.forename: Hui
authors.initials: H
authors.lastname: Deng
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
authors.forename: Gangwen
authors.initials: G
authors.lastname: Han
authors.forename: Yiqun G
authors.initials: YG
authors.lastname: Shellman
authors.forename: Steven E
authors.initials: SE
authors.lastname: Robinson
authors.forename: John J
authors.initials: JJ
authors.lastname: Tentler
authors.forename: William A
authors.initials: WA
authors.lastname: Robinson
authors.forename: David A
authors.initials: DA
authors.lastname: Norris
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Wang
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D019313:BRCA1 Protein; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D000429:Alcohol Oxidoreductases; C096794:C-terminal binding protein