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LRP-1/TbetaR-V mediates TGF-beta1-induced growth inhibition in CHO cells

Wen-Fang Tseng1, Shuan Shian Huang, Jung San Huang

  • 1Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, 1402 South Grand Boulevard, St. Louis, MO 63104, USA.

FEBS Letters
|March 27, 2004
PubMed

Insights

Low density lipoprotein receptor-related protein-1 (LRP-1), also known as type V transforming growth factor-beta (TGF-beta) receptor, is crucial for TGF-beta(1)-induced growth inhibition in CHO cells.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Type V transforming growth factor-beta (TGF-beta) receptor (TbetaR-V) is implicated in TGF-beta(1)-mediated cellular growth inhibition.
  • Recent findings identified TbetaR-V as identical to low density lipoprotein receptor-related protein-1 (LRP-1).

Purpose of the Study:

  • To investigate the role of LRP-1/TbetaR-V in TGF-beta(1)-mediated growth inhibition.
  • To confirm the functional identity of LRP-1 and TbetaR-V in cellular responses to TGF-beta(1).

Main Methods:

  • Utilized Chinese hamster ovary (CHO) cells, including wild-type and LRP-1-deficient mutant (CHO-LRP-1(-)) cells.
  • Performed stable transfection of CHO-LRP-1(-) cells with LRP-1 cDNA.
  • Investigated the effect of LRP-1 minireceptor overexpression in wild-type CHO cells.

Main Results:

  • TGF-beta(1) inhibited growth of wild-type CHO cells but not CHO-LRP-1(-) cells.
  • Restoration of LRP-1 expression in CHO-LRP-1(-) cells re-established sensitivity to TGF-beta(1)-induced growth inhibition and wild-type morphology.
  • Overexpression of LRP-1 minireceptors in wild-type CHO cells attenuated the growth inhibitory response to TGF-beta(1).

Conclusions:

  • LRP-1/TbetaR-V plays a critical role in mediating the growth inhibitory effects of TGF-beta(1) in CHO cells.
  • The findings confirm the functional significance of LRP-1 as TbetaR-V in TGF-beta(1) signaling pathways governing cell growth.

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