title: Mutation in TSC2 and activation of mammalian target of rapamycin signalling pathway in renal angiomyolipoma.
abstract: Mutations that inactivate either TSC1 or TSC2 cause tuberous sclerosis. We have used immunoblotting and immunohistochemical analysis to see whether there is phosphorylation of p70 S6 kinase, and the ribosomal S6 protein in angiomyolipomas occurring in tuberous scierosis. Hamartin (encoded by TSC1) and S6K was expressed in all samples. Tuberin (TSC2) was weak or absent in angiomyolipomas, but present in healthy kidney, whereas, phosphorylated p70 S6 kinase and p56 were present only in angiomyolipomas. Our results indicate activation of a mammalian target of rapamycin metabolic pathway in tuberous sclerosis lesions, which contributes to their growth. We suggest that treatment with rapamycin and its analogues could benefit such patients.
authors.affiliation: Brigham and Women Hospital, Department of Medicine, Haematology Division, Boston MA 02115, USA.
authors.forename: Nisreen
authors.initials: N
authors.lastname: El-Hashemite
authors.forename: Hongbing
authors.initials: H
authors.lastname: Zhang
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Henske
authors.forename: David J
authors.initials: DJ
authors.lastname: Kwiatkowski
mesh_terms: D018207:Angiomyolipoma / Q000235:genetics* / Q000473:pathology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007668:Kidney / Q000473:pathology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000473:pathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D000903:Antibiotics, Antineoplastic; D047428:Protein Kinase Inhibitors; D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; C000624651:Tsc1 protein, mouse; C000624654:Tsc2 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus