title: C. elegans and mutants with chronic nicotine exposure as a novel model of cancer phenotype.
abstract: We previously investigated MET and its oncogenic mutants relevant to lung cancer in C. elegans. The inactive orthlogues of the receptor tyrosine kinase Eph and MET, namely vab-1 and RB2088 respectively, the temperature sensitive constitutively active form of KRAS, SD551 (let-60; GA89) and the inactive c-CBL equivalent mutants in sli-1 (PS2728, PS1258, and MT13032) when subjected to chronic exposure of nicotine resulted in a significant loss in egg-laying capacity and fertility. While the vab-1 mutant revealed increased circular motion in response to nicotine, the other mutant strains failed to show any effect. Overall locomotion speed increased with increasing nicotine concentration in all tested mutant strains except in the vab-1 mutants. Moreover, chronic nicotine exposure, in general, upregulated kinases and phosphatases. Taken together, these studies provide evidence in support of C. elegans as initial in vivo model to study nicotine and its effects on oncogenic mutations identified in humans.
authors.affiliation: a Department of Medicine , Section of Hematology/Oncology, University of Chicago , Chicago , IL , USA.
authors.forename: Rajani
authors.initials: R
authors.lastname: Kanteti
authors.affiliation: a Department of Medicine , Section of Hematology/Oncology, University of Chicago , Chicago , IL , USA.
authors.forename: Immanuel
authors.initials: I
authors.lastname: Dhanasingh
authors.affiliation: b Benghazi Medical Center , Benghazi , Libya.
authors.forename: Essam
authors.initials: E
authors.lastname: El-Hashani
authors.affiliation: a Department of Medicine , Section of Hematology/Oncology, University of Chicago , Chicago , IL , USA.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Riehm
authors.affiliation: c Department of Pathology , Microbiology and Immunology, Vanderbilt University School of Medicine , Nashville , TN , USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Stricker
authors.affiliation: d Department of Physics , James Franck Institute, and the College, University of Chicago , Chicago , IL , USA.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Nagy
authors.affiliation: e Department of Surgery , Pritzker School of Medicine, University of Chicago , Chicago , IL , USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zaborin
authors.affiliation: e Department of Surgery , Pritzker School of Medicine, University of Chicago , Chicago , IL , USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Zaborina
authors.affiliation: d Department of Physics , James Franck Institute, and the College, University of Chicago , Chicago , IL , USA.
authors.forename: David
authors.initials: D
authors.lastname: Biron
authors.affiliation: e Department of Surgery , Pritzker School of Medicine, University of Chicago , Chicago , IL , USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Alverdy
authors.affiliation: f Department of Medicine , Section of Genetic Medicine, University of Chicago , Chicago , IL , USA.
authors.forename: Hae Kyung
authors.initials: HK
authors.lastname: Im
authors.affiliation: g Department of Medicine , University of Chicago, Chicago, IL and Department of Basic and Oral Biology, UQUDENT, U. Q. University , Makkah , KSA.
authors.forename: Shahid
authors.initials: S
authors.lastname: Siddiqui
authors.affiliation: h Department of Biological Sciences , University of North- Texas , Denton , TX , USA.
authors.forename: Pamela A
authors.initials: PA
authors.lastname: Padilla
authors.affiliation: a Department of Medicine , Section of Hematology/Oncology, University of Chicago , Chicago , IL , USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D005298:Fertility / Q000235:genetics; D006801:Humans; D008124:Locomotion / Q000187:drug effects / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D009538:Nicotine / Q000633:toxicity*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D018631:ras Proteins / Q000096:biosynthesis
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C095237:Sli-1 protein, C elegans; C066646:let-60 protein, C elegans; D009538:Nicotine; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; C111040:vab-1 protein, C elegans; D018631:ras Proteins
keywords: C. elegans; MET; MT13032; PS1258; PS2728; RB2088 and nicotine; SD551; vab-1