PMID- 21224066
OWN - NLM
STAT- MEDLINE
DCOM- 20110418
LR  - 20211020
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 178
IP  - 1
DP  - 2011 Jan
TI  - Enhanced epidermal growth factor, hepatocyte growth factor, and vascular 
      endothelial growth factor expression in tuberous sclerosis complex.
PG  - 296-305
LID - 10.1016/j.ajpath.2010.11.031 [doi]
AB  - Epidermal growth factor (EGF), hepatocyte growth factor (HGF), and vascular 
      endothelial growth factor (VEGF) regulate angiogenesis and cell growth in the 
      developing brain. EGF, HGF, and VEGF modulate the activity of the mammalian 
      target of rapamycin (mTOR) cascade, a pathway regulating cell growth that is 
      aberrantly activated in tuberous sclerosis complex (TSC). We hypothesized that 
      expression of EGF, HGF, VEGF, and their receptors EGFR, c-Met, and Flt-1, 
      respectively, would be altered in TSC. We show by cDNA array and 
      immunohistochemical analysis that EGF, EGFR, HGF, c-Met, and VEGF, but not Flt-1, 
      mRNA, and protein expression was up-regulated in Tsc1 conditional knockout 
      (Tsc1(GFAP)CKO) mouse cortex. Importantly, these alterations closely predicted 
      enhanced expression of these proteins in tuber and subependymal giant cell 
      astrocytoma (SEGA) specimens in TSC. Expression of EGF, EGFR, HGF, c-Met, and 
      VEGF protein, as well as hypoxia inducible factor-1alpha, a transcription factor that 
      regulates VEGF levels and is also modulated by mTOR cascade activity, was 
      enhanced in SEGAs (n = 6) and tubers (n = 10) from 15 TSC patients. Enhanced 
      expression of these growth factors and growth factor receptors in human SEGAs and 
      tubers and in the Tsc1(GFAP)CKO mouse may account for enhanced cellular growth 
      and proliferation in tubers and SEGAs and provides potential target molecules for 
      therapeutic development in TSC.
CI  - Copyright A(c) 2011 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Parker, Whitney E
AU  - Parker WE
AD  - PENN Epilepsy Center and Department of Neurology, University of Pennsylvania 
      Medical Center, Philadelphia, Pennsylvania 19104, USA.
FAU - Orlova, Ksenia A
AU  - Orlova KA
FAU - Heuer, Gregory G
AU  - Heuer GG
FAU - Baybis, Marianna
AU  - Baybis M
FAU - Aronica, Eleonora
AU  - Aronica E
FAU - Frost, Michael
AU  - Frost M
FAU - Wong, Michael
AU  - Wong M
FAU - Crino, Peter B
AU  - Crino PB
LA  - eng
GR  - R01 NS045021/NS/NINDS NIH HHS/United States
GR  - NS045021/NS/NINDS NIH HHS/United States
GR  - NS045877/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20101223
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (RNA, Messenger)
RN  - 0 (TSC1 protein, human)
RN  - 0 (Tsc1 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
SB  - IM
MH  - Animals
MH  - Brain
MH  - Cerebral Cortex/metabolism
MH  - Child
MH  - Epidermal Growth Factor/*biosynthesis/genetics
MH  - Female
MH  - Hepatocyte Growth Factor/*biosynthesis/genetics
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Oligonucleotide Array Sequence Analysis
MH  - Phosphorylation
MH  - RNA, Messenger/biosynthesis/genetics
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Tuberous Sclerosis/genetics/*metabolism
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tumor Suppressor Proteins/genetics
MH  - Vascular Endothelial Growth Factor A/*biosynthesis/genetics
PMC - PMC3069836
EDAT- 2011/01/13 06:00
MHDA- 2011/04/19 06:00
PMCR- 2012/01/01
CRDT- 2011/01/13 06:00
PHST- 2010/03/19 00:00 [received]
PHST- 2010/08/03 00:00 [revised]
PHST- 2010/09/21 00:00 [accepted]
PHST- 2011/01/13 06:00 [entrez]
PHST- 2011/01/13 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
PHST- 2012/01/01 00:00 [pmc-release]
AID - S0002-9440(10)00078-7 [pii]
AID - AJPA77 [pii]
AID - 10.1016/j.ajpath.2010.11.031 [doi]
PST - ppublish
SO  - Am J Pathol. 2011 Jan;178(1):296-305. doi: 10.1016/j.ajpath.2010.11.031. Epub 
      2010 Dec 23.