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Transforming growth factor‐β‐mediated autocrine growth regulation of gliomas as detected with phosphorothioate antisense oligonucleotides
Author(s) -
Jachimczak Piotr,
Hessdörfer Birgit,
FabelSchulte Klaus,
Wismeth Cäcilie,
Brysch Wolfgang,
Schlingensiepen KarlHermann,
Bauer Albrecht,
Blesch Armin,
Bogdahn Ulrich
Publication year - 1996
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(19960126)65:3<332::aid-ijc10>3.0.co;2-c
Subject(s) - autocrine signalling , glioma , cell growth , transforming growth factor , microbiology and biotechnology , cell culture , biology , antisense rna , extracellular , cancer research , messenger rna , gene , biochemistry , genetics
Transforming growth factors‐β1 and ‐β2 (TGF‐β1 and ‐β2) are important growth‐regulatory proteins for astroglial neoplasms. We analyzed their role in tumor‐cell proliferation in 12 glioma cell lines, employing phosphorothioate antisense oligodeoxynucleotides (S‐ODNs, 14 mer), specifically targeted against the coding sequences of TGF‐β1‐mRNA and TGF‐β2‐mRNA. TGF‐β1‐S‐ODNs inhibited cell proliferation in 5 of 12 gliomas, whereas TGF‐β2‐S‐ODNs reduced the cell proliferation in all glioma cell lines, compared to nonsense‐S‐ODN‐treated and S‐ODN‐untreated cells as controls. The efficacy and specificity of antisense effects was validated by Northern‐blot analysis and determination of protein concentrations in culture supernatants (ELISA). Exogenous hrTGF‐β1 either stimulated or inhibited the cell lines, whereas pnTGF‐β2 stimulated the proliferation of most glioma cells. Blocking the extracellular pathway of TGF‐β by neutralizing antibodies only slightly inhibited those cell lines, which were markedly stimulated by TGF‐βs. As the effects of TGF‐β2‐S‐ODNs were much stronger than those of TGF‐β neutralizing antibodies, we postulate that the endogenously produced TGF‐β2 control glioma‐cell proliferation, in part by an intracellular loop. © 1996 Wiley‐Liss, Inc.