Brain tumor formation in tuberous sclerosis depends on Erk activation.
Tuberous sclerosis (TS) is an autosomal dominant disease associated with the formation of usually benign tumors or hamartomas. The disease is connected with upregulation of mammalian target of rapamycin, central regulator of protein translation, which is usually regarded to be activated by Akt kinase. Here, we show for the first time that in all four brain lesions and one angiomyolipoma from TS patients both extracellular signal-regulated kinase (Erk) and p90 ribosomal S6 kinase 1 activation as well as Erk-dependent phosphorylation of p70 ribosomal S6 kinase 1 are markedly elevated whereas Akt, participating in the classical pathway of mammalian target of rapamycin activation is not always activated. Erk activation is also present in TS-derived cell lines. Importantly, Erk inhibition leads to the decrease of proliferation potential of such lines. These results show that Erk is specifically implicated in the pathogenesis of hamartomas.
Jozwiak
Jaroslaw
J
Department of Histology and Embryology, Center for Biostructure Research, Medical University of Warsaw, and Department of Pathology, The Children's Memorial Health Institute, Warsaw, Poland.
Grajkowska
Wieslawa
W
Kotulska
Katarzyna
K
Jozwiak
Sergiusz
S
Zalewski
Wojciech
W
Zajaczkowska
Agnieszka
A
Roszkowski
Marcin
M
Slupianek
Artur
A
Wlodarski
Pawel
P
D018207:Angiomyolipoma / Q000201:enzymology / Q000473:pathology; D000818:Animals; D001254:Astrocytoma / Q000201:enzymology / Q000473:pathology; D001932:Brain Neoplasms / Q000201:enzymology* / Q000473:pathology; D002070:Butadienes / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009570:Nitriles / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000201:enzymology / Q000473:pathology*
D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; C113580:U 0126; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases