Tuberin-heterozygous cell line TSC2ang1 as a model for tuberous sclerosis-associated skin lesions.
نویسندگان
چکیده
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.
منابع مشابه
Tuberous sclerosis-associated neoplasms express activated p42/44 mitogen-activated protein (MAP) kinase, and inhibition of MAP kinase signaling results in decreased in vivo tumor growth.
PURPOSE Tuberous sclerosis (TS) is a common autosomal disorder attributable to inactivation of the tumor suppressor genes tuberin and hamartin. To determine whether mitogen-activated protein (MAP) kinase signaling plays a role in the pathogenesis of TS, we stained human TS-associated neoplasms with antibodies directed against activated MAP kinase, and observed high-level expression. EXPERIMEN...
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Tuberous sclerosis complex (TSC) is a tumour suppressor gene syndrome whose manifestations include seizures, mental retardation, autism, and tumours of the brain, retina, kidney, heart, and skin. Mutations in two tumour suppressor genes, TSC1 on chromosome 9q34 and TSC2 on chromosome 16p13, cause TSC. TSC2 encodes tuberin, a 190 kDa protein with homology to the catalytic domain of a GTPase acti...
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عنوان ژورنال:
- International journal of molecular medicine
دوره 21 2 شماره
صفحات -
تاریخ انتشار 2008