PMID- 18370913
OWN - NLM
STAT- MEDLINE
DCOM- 20080520
LR  - 20211203
IS  - 1539-6851 (Print)
IS  - 1539-6851 (Linking)
VI  - 5
IP  - 4
DP  - 2007
TI  - Mammalian target of rapamycin (mTOR) is activated in cutaneous vascular 
      malformations in vivo.
PG  - 233-6
LID - 10.1089/lrb.2007.1012 [doi]
AB  - 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. METHODS AND 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. CONCLUSION: 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.
FAU - Shirazi, Farheen
AU  - Shirazi F
AD  - Department of Dermatology, Emory University School of Medicine, Atlanta, GA 
      30322, USA.
FAU - Cohen, Cynthia
AU  - Cohen C
FAU - Fried, Levi
AU  - Fried L
FAU - Arbiser, Jack L
AU  - Arbiser JL
LA  - eng
GR  - P30 AR 42687/AR/NIAMS NIH HHS/United States
GR  - R01 AR 47901/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Lymphat Res Biol
JT  - Lymphatic research and biology
JID - 101163587
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Immunohistochemistry
MH  - Phosphorylation
MH  - Protein Kinases/*metabolism
MH  - Ribosomal Protein S6 Kinases/*metabolism
MH  - Sturge-Weber Syndrome/*metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2008/03/29 09:00
MHDA- 2008/05/21 09:00
CRDT- 2008/03/29 09:00
PHST- 2008/03/29 09:00 [pubmed]
PHST- 2008/05/21 09:00 [medline]
PHST- 2008/03/29 09:00 [entrez]
AID - 10.1089/lrb.2007.1012 [doi]
PST - ppublish
SO  - Lymphat Res Biol. 2007;5(4):233-6. doi: 10.1089/lrb.2007.1012.