Mammalian target of rapamycin (mTOR) is activated in cutaneous vascular malformations in vivo.
BACKGROUND
Vascular malformation signaling pathways are the least understood out of all cutaneous endothelial lesions. The overexpression of Akt is known to cause vascular malformations in endothelial cells of mice. Since there are no Akt inhibitors approved for clinical use, we examined phosphorylated S6 expression, a downstream target of Akt. Phosphorylated S6 indicates potential sensitivity to rapamycin.


RESULTS
Immunohistochemistry for phospho-s6k against phospho-S6 ribosomal protein was performed on specimens of vascular malformations taken from Sturge- Weber patients. Of the specimens, 70.8% were immunopositive for phospho-s6k.


CONCLUSIONS
Endothelial expression of Akt is responsible for tumor responsiveness to rapamycin. We demonstrate that expression of phosphorylated S6 is elevated in specimens. Our findings provide a rationale for clinical trials of rapamycin on Sturge-Weber or Klippel-Trenaunay-Weber patients.
Shirazi
Farheen
F
Department of Dermatology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cohen
Cynthia
C
Fried
Levi
L
Arbiser
Jack L
JL
D006801:Humans; D007150:Immunohistochemistry; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D013341:Sturge-Weber Syndrome / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases