PMID- 17438183
OWN - NLM
STAT- MEDLINE
DCOM- 20070524
LR  - 20161019
IS  - 0003-987X (Print)
IS  - 0003-987X (Linking)
VI  - 143
IP  - 4
DP  - 2007 Apr
TI  - AKT1 overexpression in endothelial cells leads to the development of cutaneous 
      vascular malformations in vivo.
PG  - 504-6
AB  - BACKGROUND: Vascular malformations are clinical disorders in which endothelial 
      cells fail to remodel and/or undergo programmed cell death, leading to abnormal 
      persistence of blood vessels. The abnormal persistence of vessels makes therapy 
      difficult because these lesions are resistant to interventions that are effective 
      against hemangiomas. Akt1 is a serine-threonine protein kinase, which is a key 
      mediator of resistance to programmed cell death. Our objective was to determine 
      whether sustained activation of Akt1 could lead to vascular malformation in mice. 
      OBSERVATIONS: We examined the effect of constitutive activation of Akt1 in murine 
      endothelial cells (MS1 cells). Overexpression of active AKT1 in MS1 cells led to 
      the development of vascular malformations, characterized by wide endothelial 
      lumens and minimal investment of smooth muscle surrounding the vessels. The 
      histologic features of these vascular malformations is distinct from 
      ras-transformed MS1 cells (angiosarcoma) and suggest that differing signal 
      abnormalities give rise to human vascular malformations vs malignant vascular 
      tumors. CONCLUSIONS: Inhibition of Akt signaling may be useful in the treatment 
      of vascular malformations. Examination of problematic hemangiomas and vascular 
      malformations for the presence of activated Akt or downstream targets of Akt, 
      such as mammalian target of rapamycin (mTOR), may predict response to treatment 
      with Akt inhibitors or rapamycin. This study provides a potential rationale for 
      the systemic and topical use of these inhibitors for vascular malformations and 
      hemangiomas.
FAU - Perry, Betsy
AU  - Perry B
AD  - Department of Dermatology, Emory University School of Medicine, Atlanta, GA 
      30322, USA.
FAU - Banyard, Jacqueline
AU  - Banyard J
FAU - McLaughlin, Elizabeth R
AU  - McLaughlin ER
FAU - Watnick, Randy
AU  - Watnick R
FAU - Sohn, Allie
AU  - Sohn A
FAU - Brindley, David N
AU  - Brindley DN
FAU - Obata, Toshiyuki
AU  - Obata T
FAU - Cantley, Lewis C
AU  - Cantley LC
FAU - Cohen, Cynthia
AU  - Cohen C
FAU - Arbiser, Jack L
AU  - Arbiser JL
LA  - eng
GR  - R01 GM041890/GM/NIGMS NIH HHS/United States
GR  - P30 AR42687/AR/NIAMS NIH HHS/United States
GR  - R01 AR47901/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  - Arch Dermatol
JT  - Archives of dermatology
JID - 0372433
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - Blood Vessels/*abnormalities
MH  - Cell Line
MH  - Endothelial Cells/metabolism/transplantation
MH  - Endothelium, Vascular/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Skin/*blood supply
EDAT- 2007/04/18 09:00
MHDA- 2007/05/26 09:00
CRDT- 2007/04/18 09:00
PHST- 2007/04/18 09:00 [pubmed]
PHST- 2007/05/26 09:00 [medline]
PHST- 2007/04/18 09:00 [entrez]
AID - 143/4/504 [pii]
AID - 10.1001/archderm.143.4.504 [doi]
PST - ppublish
SO  - Arch Dermatol. 2007 Apr;143(4):504-6. doi: 10.1001/archderm.143.4.504.