PMID- 16129702
OWN - NLM
STAT- MEDLINE
DCOM- 20060227
LR  - 20220309
IS  - 0022-1007 (Print)
IS  - 1540-9538 (Electronic)
IS  - 0022-1007 (Linking)
VI  - 202
IP  - 5
DP  - 2005 Sep 5
TI  - MCP-1 overexpressed in tuberous sclerosis lesions acts as a paracrine factor for 
      tumor development.
PG  - 617-24
AB  - Patients with tuberous sclerosis complex (TSC) develop hamartomatous tumors 
      showing loss of function of the tumor suppressor TSC1 (hamartin) or TSC2 
      (tuberin) and increased angiogenesis, fibrosis, and abundant mononuclear 
      phagocytes. To identify soluble factors with potential roles in TSC 
      tumorigenesis, we screened TSC skin tumor-derived cells for altered gene and 
      protein expression. Fibroblast-like cells from 10 angiofibromas and five 
      periungual fibromas produced higher levels of monocyte chemoattractant protein-1 
      (MCP-1) mRNA and protein than did fibroblasts from the same patient's normal 
      skin. Conditioned medium from angiofibroma cells stimulated chemotaxis of a human 
      monocytic cell line to a greater extent than conditioned medium from TSC 
      fibroblasts, an effect blocked by neutralizing MCP-1-specific antibody. 
      Overexpression of MCP-1 seems to be caused by loss of tuberin function because 
      Eker rat embryonic fibroblasts null for Tsc2 (EEF Tsc2(-/-)) produced 28 times as 
      much MCP-1 protein as did EEF Tsc2(+/+) cells; transient expression of WT but not 
      mutant human TSC2 by EEF Tsc2(-/-) cells inhibited MCP-1 production; and 
      pharmacological inhibition of the Rheb-mTOR pathway, which is hyperactivated 
      after loss of TSC2, decreased MCP-1 production by EEF Tsc2(-/-) cells. Together 
      these findings suggest that MCP-1 is an important paracrine factor for TSC 
      tumorigenesis and may be a new therapeutic target.
FAU - Li, Shaowei
AU  - Li S
AD  - Department of Dermatology, Uniformed Services University of the Health Sciences, 
      Bethesda, MD 20814, USA.
FAU - Takeuchi, Fumiko
AU  - Takeuchi F
FAU - Wang, Ji-an
AU  - Wang JA
FAU - Fuller, Christopher
AU  - Fuller C
FAU - Pacheco-Rodriguez, Gustavo
AU  - Pacheco-Rodriguez G
FAU - Moss, Joel
AU  - Moss J
FAU - Darling, Thomas N
AU  - Darling TN
LA  - eng
GR  - R01 CA100907/CA/NCI NIH HHS/United States
GR  - 1 R01 CA100907/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20050829
PL  - United States
TA  - J Exp Med
JT  - The Journal of experimental medicine
JID - 2985109R
RN  - 0 (Antibodies)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Tsc2 protein, rat)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Antibodies/metabolism
MH  - Chemokine CCL2/*metabolism
MH  - Chemotaxis/drug effects
MH  - Culture Media, Conditioned/pharmacology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Fibroblasts/metabolism
MH  - Fibroma/etiology/*metabolism
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Immunohistochemistry
MH  - Oligonucleotide Array Sequence Analysis
MH  - Paracrine Communication/*drug effects
MH  - Rats
MH  - Tuberous Sclerosis/complications/*metabolism
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Cells, Cultured
MH  - Tumor Suppressor Proteins/genetics/metabolism
PMC - PMC1378109
MID - NIHMS7508
EDAT- 2005/09/01 09:00
MHDA- 2006/02/28 09:00
PMCR- 2006/03/05
CRDT- 2005/09/01 09:00
PHST- 2005/09/01 09:00 [pubmed]
PHST- 2006/02/28 09:00 [medline]
PHST- 2005/09/01 09:00 [entrez]
PHST- 2006/03/05 00:00 [pmc-release]
AID - jem.20042469 [pii]
AID - 20042469 [pii]
AID - 10.1084/jem.20042469 [doi]
PST - ppublish
SO  - J Exp Med. 2005 Sep 5;202(5):617-24. doi: 10.1084/jem.20042469. Epub 2005 Aug 29.