Identification of cadherin-11 down-regulation as a common response of astrocytoma cells to transforming growth factor-alpha

Differentiation. 2000 Dec;66(4-5):165-72. doi: 10.1046/j.1432-0436.2000.660402.x.


Transforming growth factor-alpha (TGF-alpha) and its receptor are frequently co-expressed in high-grade astrocytomas, suggesting a role for TGF-alpha autocrine/paracrine loops in the malignant progression of astrocytomas. To identify genes that may be critical in mediating TGF-alpha impact on the malignant progression of astrocytomas, we have used cDNA arrays to investigate TGF-alpha effects on the gene expression profile of U-373 MG glioblastoma cells. We found that in these cells approximately 50% of the TGF-alpha regulated genes code for cell motility/invasion-related proteins. TGF-alpha action on the expression of four of these proteins, alpha-catenin, IQGAP1, RhoA, and cadherin-11, was further investigated by immunoblotting in four astrocytoma cell lines and in normal astrocytes. The results demonstrate that the effects of TGF-alpha on IQGAP1, alpha-catenin, and RhoA expression are cell-line dependent. On the other hand, under TGF-alpha treatment, cadherin-11 expression is consistently decreased in all astrocytoma cell lines tested but is increased in normal astrocytes. In addition, we found that cadherin-11 is consistently down-regulated in astrocytomas versus normal brain tissues. Altogether, these results suggest that the down-regulation of cadherin-11 is a frequent molecular event in the neoplastic transformation of astrocytes and that this down-regulation may be initiated and/or amplified by TGF-alpha autocrine/paracrine loops during tumor progression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytoma / genetics*
  • Astrocytoma / metabolism*
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / metabolism*
  • Cadherins / biosynthesis*
  • Cadherins / genetics*
  • Cell Transformation, Neoplastic
  • Down-Regulation / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glioblastoma
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Recombinant Proteins / pharmacology
  • Transforming Growth Factor alpha / pharmacology*


  • Cadherins
  • Recombinant Proteins
  • Transforming Growth Factor alpha
  • osteoblast cadherin