Expression of transforming-growth-factor (TGF)-β receptors and Smad proteins in glioblastoma cell lines with distinct responses to TGF-β1

✍ Scribed by Ester Piek; Ulrica Westermark; Marianne Kastemar; Carl-Henrik Heldin; E. Joop van Zoelen; Monica Nistér; Peter Ten Dijke

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: French
• Weight: 268 KB
• Volume: 80
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/(sici)1097-0215(19990301)80:5<756::aid-ijc21>3.0.co;2-n

✦ Synopsis

A panel of 6 human glioma cell lines was examined for TGF-␤1 responsiveness. U-178 MG and U-251 MG AgCl1 were significantly inhibited by TGF-␤1, while U-343 MGa 31L and U-343 MGa 35L were potently stimulated to proliferate. TGF-␤1 induced endogenous PAI-1 protein synthesis, Smad binding element/(CAGA) 12 -luciferase-reporter activity, as well as mRNA expression of Smad6 and Smad7 in all gliomas. Interestingly, TGF-␤1 differentially stimulated or inhibited the expression of T␤R-I and T␤R-II mRNA in the gliomas. Affinity cross-linking studies using 125 I-TGF-␤1 revealed that the gliomas expressed TGF-␤-type-I(T␤R-I) and -type-II(T␤R-II) receptors, although binding to T␤R-II in U-343 MGa 31L and U-251 MG AgCl1 was low to undetectable. Smad2 protein was abundantly present in U-178 MG, U-343 MG, and U-343 MGa 35L, while Smad3 was readily detectable in U-178 MG, U-343 MG, U-343 MGa 35L and U-251 MG AgCl1. In all gliomas, TGF-␤1 induced phosphorylation of Smad2. The level to which TGF-␤1 could activate the pathway leading to induction of the (CAGA) 12 -luciferase reporter seemed to correlate to the expression levels of TGF-␤ receptors, Smad3 and Smad4 proteins. However, despite the plethora of data regarding TGF-␤1 signalling in the different glioma cell lines, the mechanism underlying the differential growth effects mediated by TGF-␤1 is still unclear. The results suggest that a complex balance between several components in the TGF-␤ signalling pathway controls glioma responsiveness to TGF-␤1, and extend reports indicating that distinct signal transduction pathways are involved in growth inhibition and other cellular responses.