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Title: Expression of Caveolin-1 reduces cellular responses to TGF-{beta}1 through down-regulating the expression of TGF-{beta} type II receptor gene in NIH3T3 fibroblast cells

Transcriptional repression of Transforming Growth Factor-{beta} type II receptor (T{beta}RII) gene has been proposed to be one of the major mechanisms leading to TGF-{beta} resistance. In this study, we demonstrate that expression of Caveolin-1 (Cav-1) gene in NIH3T3 fibroblast cells down-regulates the expression of T{beta}RII gene in the transcriptional level, eventually resulting in the decreased responses to TGF-{beta}. The reduced expression of T{beta}RII gene by Cav-1 appeared to be due to the changes of the sequence-specific DNA binding proteins to either Positive Regulatory Element 1 (PRE1) or PRE2 of the T{beta}RII promoter. In addition, Cav-1 expression inhibited TGF-{beta}-mediated cellular proliferation and Plasminogen Activator Inhibitor (PAI)-1 gene expression as well as TGF-{beta}-induced luciferase activity. Furthermore, the inhibition of endogeneous Cav-1 by small interfering RNA increased the expression of T{beta}RII gene. These findings strongly suggest that expression of Cav-1 leads to the decreased cellular responsiveness to TGF-{beta} through down-regulating T{beta}RII gene expression.
Authors:
 [1] ;  [2] ;  [1] ;  [3]
  1. Inha University College of Medicine, Incheon 400-121 (Korea, Republic of)
  2. Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)
  3. Inha University College of Medicine, Incheon 400-121 (Korea, Republic of) and Department of Biological Science, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of). E-mail: parks@skku.edu
Publication Date:
OSTI Identifier:
20991460
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 359; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2007.05.121; PII: S0006-291X(07)01102-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL PROLIFERATION; DNA; FIBROBLASTS; GENES; GROWTH FACTORS; INHIBITION; LUCIFERASE; PLASMINOGEN; PROMOTERS; RECEPTORS; RNA