title: Tuberin-heterozygous cell line TSC2ang1 as a model for tuberous sclerosis-associated skin lesions.
abstract: Tuberous sclerosis (TS), neurological disorder manifesting with the formation of tumors in numerous organ systems, is a disease associated with the upregulation of mammalian target of rapamycin (mTOR) pathway. It has been found that in healthy individuals two tumor suppressor genes, TSC1 and TSC2, encoding proteins called hamartin and tuberin, respectively, are responsible for the control over mTOR kinase. Loss of one of these genes constitutes the genetic background of TS. In the current study, we aimed at evaluating the fitness of the only TS-associated sarcoma cell line deposited in American Tissue Culture Collection, TSC2ang1, for the in vitro studies on TS. We found that the line shows a stable chromosome pattern with typical Robertsonian translocations. Similarly to primary tumors from TS patients, TSC2ang1 cells respond to rapamycin-induced mTOR inhibition. The cells demonstrate activation of both Akt and Erk pathways, but inhibition of neither of them is as effective as mTOR suppression when considering proliferation potential. Based on these results we propose TSC2ang1 as a good and stable model for pathophysiological and pharmacological studies on skin lesions in TS.
authors.affiliation: Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, Poland.
authors.forename: Pawel K
authors.initials: PK
authors.lastname: Wlodarski
authors.forename: Radoslaw
authors.initials: R
authors.lastname: Maksym
authors.forename: Monika
authors.initials: M
authors.lastname: Oldak
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jozwiak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wojcik
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Jozwiak
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D016466:CHO Cells; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D002877:Chromosomes, Human; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D006579:Heterozygote; D006801:Humans; D007621:Karyotyping; D009025:Morpholines / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology / Q000473:pathology*; D013379:Substrate Specificity / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000201:enzymology / Q000473:pathology*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002070:Butadienes; D002867:Chromones; D009025:Morpholines; D009570:Nitriles; D000081082:Phosphoinositide-3 Kinase Inhibitors; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C113580:U 0126; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D000077191:Wortmannin