title: Identification of Down's syndrome critical locus gene SIM2-s as a drug therapy target for solid tumors.
abstract: We report here a cancer drug therapy use of a gene involved in Down's syndrome. Using bioinformatics approaches, we recently predicted Single Minded 2 gene (SIM2) from Down's syndrome critical region to be specific to certain solid tumors. Involvement of SIM2 in solid tumors has not previously been reported. Intrigued by a possible association between a Down's syndrome gene and solid tumors, we monitored SIM2 expression in solid tumors. Isoform-specific expression of SIM2 short-form (SIM2-s) was seen selectively in colon, prostate, and pancreatic carcinomas but not in breast, lung, or ovarian carcinomas nor in most normal tissues. In colon tumors, SIM2-s expression was seen in early stages. Antisense inhibition of SIM2-s expression in a colon cancer cell line caused inhibition of gene expression, growth inhibition, and apoptosis. The administration of the antisense, but not the control, oligonucleotides caused a pronounced inhibition of tumor growth in nude mice with no major toxicity. Our findings provide a strong rationale for the genes-to-drugs paradigm, establish SIM2-s as a molecular target for cancer therapeutics, and may further understanding of the cancer risk of Down's syndrome patients.
authors.affiliation: Center for Molecular Biology and Biotechnology and Department of Biology, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA.
authors.forename: Maurice Phil
authors.initials: MP
authors.lastname: DeYoung
authors.forename: Matthew
authors.initials: M
authors.lastname: Tress
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Narayanan
mesh_terms: D000818:Animals; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D004314:Down Syndrome / Q000235:genetics*; D029721:Drosophila Proteins; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000627:therapeutic use; D009857:Oncogenes; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018076:DNA, Complementary; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D020033:Protein Isoforms; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C417032:SIM2 protein, human; C089449:sim protein, Drosophila