Cellular growth inhibition by IGFBP-3 and TGF-β1 requires LRP-1

Shuan Shian Huang, Thai Yen Ling, Wen Fang Tseng, Yen Hwa Huang, Fen Mei Tang, Sandra M. Leal, Jung San Huang

研究成果: 雜誌貢獻文章同行評審

132 引文 斯高帕斯(Scopus)


The type V TGF-β receptor (TβR-V)/ IGFBP-3 receptor mediates the IGF-independent growth inhibition induced by IGFBP-3. It also mediates the growth inhibitory response to TGF-β1 in concert with other TGF-β receptor types, and its loss may contribute to the malignant phenotype of human carcinoma cells. Here we demonstrate that TβR-V is identical to LRP-1/α2M receptor as shown by MALDI-TOF analysis of tryptic peptides of TβR-V purified from bovine liver. In addition, 125I-IGFBP-3 affinity-labeled TβR-V in Mv1Lu cells is immunoprecipitated by antibodies to LRP-1 and TβR-V. RAP, an LRP-1 antagonist, inhibits binding of 125I-TGF-β1 and 125I-IGFBP-3 to TβR-V and diminishes IGFBP-3-induced growth inhibition in Mv1Lu cells. Absent or low levels of LRP-1, as with TβR-V, have been linked to the malignant phenotype of carcinoma cells. Mutagenized Mv1Lu cells selected for reduced expression of LRP-1 have an attenuated growth inhibitory response to TGF-β1 and IGFBP-3. LRP-1-deficient mouse embryonic fibroblasts lack a growth inhibitory response to TGF-β 1 and IGFBP-3. On the other hand, stable transfection of H1299 human lung carcinoma cells with LRP-1 cDNA restores the growth inhibitory response. These results suggest that the LRP-1/TβR-V/IGFBP-3 receptor is required for the growth inhibitory response to IGFBP-3 and TGF-β1.

頁(從 - 到)2068-2081
期刊FASEB Journal
出版狀態已發佈 - 十一月 2003

ASJC Scopus subject areas

  • 農業與生物科學(雜項)
  • 生物化學、遺傳與分子生物學 (全部)
  • 生物化學
  • 細胞生物學


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