Cardiac rhabdomyoma in tuberous sclerosis: hyperactive Erk signaling.
Tuberous sclerosis (TS) is a neurological disorder associated with the formation of tumors in several organs. Cardiac rhabdomyomas are possibly the earliest symptom of TS. Although rhabdomyomas are present in about half of TS patients, little is known of their molecular background since these tumors are rarely resected. Here we present a patient diagnosed with TS, in whom rhabdomyoma has been excised due to deterioration of hemodynamics. We found, that the tumor remained heterozygous for the affected TSC2 gene. To analyze molecular mechanisms implicated in rhabdomyoma growth, we determined the status of mTOR, Akt and Erk pathways. We found that Akt was not upregulated, while mTOR, Erk and its substrates were hyperactive. Classic activator of Erk, MEK, was only modestly active. We hypothesize that rhabdomyoma arising in TS may progress due to Erk potentiation.
Jozwiak
Jaroslaw
J
Sahin
Mustafa
M
Jozwiak
Sergiusz
S
Kotulska
Katarzyna
K
Ploski
Rafal
R
Szperl
Malgorzata
M
Wlodarski
Pawel K
PK
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D002675:Child, Preschool; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006338:Heart Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D012207:Rhabdomyoma / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000150:complications* / Q000235:genetics; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics
C486377:AKTIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D047908:Intracellular Signaling Peptides and Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases