Induction of apoptosis by transforming growth factor beta 1 in glioma and trigeminal neurinoma cells.
Transforming growth factor beta 1 (TGF beta 1) inhibits cell proliferation in T24 glioma and 476-16 trigeminal neurinoma (Schwannoma) cells. In both cell types, the inhibition of cell proliferation is followed by cell rounding and detachment as well as internucleosomal DNA fragmentation, nuclear condensation and cell shrinkage, cellular changes that are characteristic for apoptosis. While the induction of apoptosis is closely coupled with the inhibition of cell proliferation in these tumor cells, the mode of apoptosis appears to differ between the two cell types. In 476-16 cells whose proliferation is highly susceptible to TGF beta 1, apoptosis occurs primarily after growth arrest at the G1 phase. Apoptotic cell death of 476-16 cells pretreated with TGF beta 1 is stimulated by serum deprivation, and it is inhibited by mitogenic growth factors such as insulin and platelet-derived growth factors. In T24 cells whose DNA replication is inhibited only moderately by TGF beta 1, apoptosis occurs in the presence of TGF beta 1 during the final cell division cycle when cells undergo density-induced growth arrest. While staurosporine accelerates TGF beta 1-induced apoptosis in both 476-16 and T24 cells, 12-O-tetradecanoylphorbol 13-acetate inhibits TGF beta 1-induced apoptosis of 476-16 cells but stimulates that of T24 cells. The present results suggest that TGF beta 1 may potentially be utilized for the management of neurogenic tumors of glial and Schwann cell origin.
Marushige
K
K
Department of Pathology, Michigan State University, East Lansing 48824.
Marushige
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects; D003390:Cranial Nerve Neoplasms; D004273:DNA, Neoplasm / Q000032:analysis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005910:Glioma; D007700:Kinetics; D009442:Neurilemmoma; D051381:Rats; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014276:Trigeminal Nerve; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D016212:Transforming Growth Factor beta