title: Cardiac rhabdomyomas in tuberous sclerosis complex show apoptosis regulation and mTOR pathway abnormalities.
abstract: Cardiac rhabdomyoma (CR) is the most common heart tumor in children and is usually associated with tuberous sclerosis complex (TSC). Tuberous sclerosis complex is a genetic disorder caused by a mutation in either of 2 genes (TSC1 or TSC2) and characterized by the formation of hamartomas in multiple organs. The 2 TSC proteins, hamartin and tuberin, antagonize the mammalian target of rapamycin (mTOR) signaling pathway, thus regulating cell growth and proliferation. Recently, some trials treating TSC with the mTOR inhibitor rapamycin have been published; however, the impact of such treatment on heart tumors is not known. The aim of the present paper was to study the molecular pathobiology of CRs. Six CR samples were studied. The expression of S6K1, pErk, Erk, Akt, pAkt, 4E-BP1, hamartin, tuberin, mTOR, bcl-2, Bax, and Ki-67 was examined using immunohistochemistry and Western blot methods. Increased expression of Bax, mTOR, pS6K, pErk, and 4E-BP1 was found in all CR samples. Hamartin and tuberin expression was decreased in tumors versus normal heart tissues. This is the first study showing mTOR pathway dysregulation and an increased expression of proapoptotic Bax protein in CRs associated with TSC.
authors.affiliation: Department of Neurology and Epileptology, The Children's Memorial Health Institute, Warsaw, Poland. k.kotulska@czd.pl
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kotulska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Larysz-Brysz
authors.forename: Wieslława
authors.initials: W
authors.lastname: Grajkowska
authors.forename: Jarosław
authors.initials: J
authors.lastname: Jóźwiak
authors.forename: Paweł
authors.initials: P
authors.lastname: Włodarski
authors.forename: Mustafa
authors.initials: M
authors.lastname: Sahin
authors.forename: Joanna
authors.initials: J
authors.lastname: Lewin-Kowalik
authors.forename: Dorota
authors.initials: D
authors.lastname: Domańska-Pakieła
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jóźwiak
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D002675:Child, Preschool; D019084:Fluorescent Antibody Technique, Indirect; D006338:Heart Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011494:Protein Kinases / Q000378:metabolism*; D012207:Rhabdomyoma / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D058570:TOR Serine-Threonine Kinases; D014402:Tuberous Sclerosis / Q000150:complications / Q000378:metabolism / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases