Identification of cadherin-11 down-regulation as a common response of astrocytoma cells to transforming growth factor-alpha.
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.
Department of Anatomy and Cell Biology, University of Illinois at Chicago, 808 S. Wood Street, M/C 512 Chicago, IL 60612, USA.
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D000818:Animals; D001254:Astrocytoma / Q000235:genetics* / Q000378:metabolism*; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism*; D015820:Cadherins / Q000096:biosynthesis* / Q000235:genetics*; D002471:Cell Transformation, Neoplastic; D015536:Down-Regulation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000494:pharmacology*
D015820:Cadherins; D011994:Recombinant Proteins; D016211:Transforming Growth Factor alpha; C086960:osteoblast cadherin