title: FOXD3 Promotes PAX3 Expression in Melanoma Cells.
abstract: Several key transcription factors regulate cell growth, survival, and differentiation during neural crest and melanoblast development in the embryo, and these same pathways may be reactivated in tumors arising from the progenitors of these cells. The transcription factors PAX3 and FOXD3 have essential roles in melanoblasts and melanoma. In this study, we define a regulatory pathway where FOXD3 promotes the expression of PAX3. Both factors are expressed in melanoma cells and there is a positive correlation between the transcript levels of PAX3 and FOXD3. The PAX3 gene contains two FOX binding motifs within highly conserved enhancer regulatory elements that are essential for neural crest development. FOXD3 binds to both of these motifs in vitro but only one of these sites is preferentially utilized in melanoma cells. Overexpression of FOXD3 upregulates PAX3 levels while inhibition of FOXD3 function does not alter PAX3 protein levels, supporting that FOXD3 is sufficient but not necessary to drive PAX3 expression in melanoma cells. Here, we identify a molecular pathway where FOXD3 upregulates PAX3 expression and therefore contributes to melanoma progression.
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, 60637.
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Kubic
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, 60637.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Little
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, 60637.
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Kaiser
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, 60637.
authors.forename: Kacey P
authors.initials: KP
authors.lastname: Young
authors.affiliation: Department of Medicine, Section of Dermatology, University of Chicago, Chicago, Illinois, 60637.
authors.forename: Deborah
authors.initials: D
authors.lastname: Lang
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D017124:Conserved Sequence; D051858:Forkhead Transcription Factors / Q000502:physiology*; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma; D008969:Molecular Sequence Data; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015533:Transcriptional Activation
chemical_list: C503514:FOXD3 protein, human; D051858:Forkhead Transcription Factors; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors
keywords: DNA-PROTEIN INTERACTION; FOXD3; GENE REGULATION; MELANOMA; PAX3; TRANSCRIPTION FACTORS