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Expression of transforming‐growth‐factor (TGF)‐β receptors and Smad proteins in glioblastoma cell lines with distinct responses to TGF‐β1
Author(s) -
Piek Ester,
Westermark Ulrica,
Kastemar Marianne,
Heldin CarlHenrik,
van Zoelen E. Joop,
Nistér Monica,
Ten Dijke Peter
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990301)80:5<756::aid-ijc21>3.0.co;2-n
Subject(s) - smad , transforming growth factor , receptor , biology , smad2 protein , signal transduction , microbiology and biotechnology , cell culture , glioma , r smad , cell growth , endocrinology , growth factor , cancer research , medicine , tgf alpha , biochemistry , genetics
A panel of 6 human glioma cell lines was examined for TGF‐β1 responsiveness. U‐178 MG and U‐251 MG AgCl1 were significantly inhibited by TGF‐β1, while U‐343 MGa 31L and U‐343 MGa 35L were potently stimulated to proliferate. TGF‐β1 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‐β1 differentially stimulated or inhibited the expression of T β R‐I and T β R‐II mRNA in the gliomas. Affinity cross‐linking studies using 125 I‐TGF‐β1 revealed that the gliomas expressed TGF‐β‐type‐I(TβR‐I) and ‐type‐II(TβR‐II) receptors, although binding to TβR‐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‐β1 induced phosphorylation of Smad2. The level to which TGF‐β1 could activate the pathway leading to induction of the (CAGA) 12 ‐luciferase reporter seemed to correlate to the expression levels of TGF‐β receptors, Smad3 and Smad4 proteins. However, despite the plethora of data regarding TGF‐β1 signalling in the different glioma cell lines, the mechanism underlying the differential growth effects mediated by TGF‐β1 is still unclear. The results suggest that a complex balance between several components in the TGF‐β signalling pathway controls glioma responsiveness to TGF‐β1, and extend reports indicating that distinct signal transduction pathways are involved in growth inhibition and other cellular responses. Int. J. Cancer 80:756–763, 1999. © 1999 Wiley‐Liss, Inc.