title: Sequencing and G-quadruplex folding of the canine proto-oncogene KIT promoter region: might dog be used as a model for human disease?
abstract: Downregulation of gene expression by induction of non-canonical DNA structures at promotorial level is a novel attractive anticancer strategy. In human, two guanine-rich sequences (h_kit1 and h_kit2) were identified in the promotorial region of oncogene KIT. Their stabilization into G-quadruplex structures can find applications in the treatment of leukemias, mastocytosis, gastrointestinal stromal tumor, and lung carcinomas which are often associated to c-kit mis-regulation. Also the most common skin cancer in domestic dog, mast cell tumor, is linked to a mutation and/or to an over-expression of c-kit, thus supporting dog as an excellent animal model. In order to assess if the G-quadruplex mediated mechanism of regulation of c-kit expression is conserved among the two species, herein we cloned and sequenced the canine KIT promoter region and we compared it with the human one in terms of sequence and conformational equilibria in physiologically relevant conditions. Our results evidenced a general conserved promotorial sequence between the two species. As experimentally confirmed, this grants that the conformational features of the canine kit1 sequence are substantially shared with the human one. Conversely, two isoforms of the kit2 sequences were identified in the analyzed dog population. In comparison with the human counterpart, both of them showed an altered distribution among several folded conformations.
authors.affiliation: Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova (PD), Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Da Ros
authors.affiliation: Dept. of Comparative Biomedicine and Food Science, University of Padova, Legnaro (PD), Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Zorzan
authors.affiliation: Dept. of Comparative Biomedicine and Food Science, University of Padova, Legnaro (PD), Italy.
authors.forename: Mery
authors.initials: M
authors.lastname: Giantin
authors.affiliation: Dept. of Comparative Biomedicine and Food Science, University of Padova, Legnaro (PD), Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Zorro Shahidian
authors.affiliation: Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova (PD), Italy.
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
authors.affiliation: Dept. of Comparative Biomedicine and Food Science, University of Padova, Legnaro (PD), Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Dacasto
authors.affiliation: Dept. of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova (PD), Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sissi
mesh_terms: D000818:Animals; D004285:Dogs; D054856:G-Quadruplexes; D006801:Humans; D011401:Promoter Regions, Genetic / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit
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