Induction of platelet-derived growth factor B/c-sis by the v-erbA oncogene in glial cells.
The v-erbA oncogene codes for a mutated form of the thyroid hormone receptor TR/c-erbA-alpha. Thyroid hormone (triiodothyronine, T3) regulates glial functions such as myelination and both astrocytes and oligodendrocytes have been shown to express thyroid hormone receptors (TRs). To study putative effects of v-erbA on glial precursors, we have expressed it in a glial clonal cell line established from early embryonal mouse brain. We have found that v-erbA increases cell survival in serum-free conditions. Moreover, v-erbA-expressing cells show a substantial growth in the presence of insulin or IGF-I, whereas normal and TR/c-erbA-over-expressing cells progressively degenerate. By Northern blotting, immunofluorescence, immunoprecipitation, and neutralization experiments, we show that v-erbA actions are mediated by an increase in the levels of PDGF B/c-sis mRNA and protein. We used anti-PDGF receptor and anti-phosphotyrosine antibodies to show the constitutive activation of PDGF receptors in B3.1 + v-erbA cells, and neutralizing anti-PDGF antibodies to demonstrate that v-erbA enhances the secretion of active PDGF into the culture medium. Our data indicate that v-erbA induces PDGF B/c-sis, a factor involved in the generation of gliomas, the most common central nervous system tumor in humans.
Iglesias
T
T
Instituto de Investigaciones Biomédicas, C.S.I.C., Madrid, Spain.
Llanos
S
S
López-Barahona
M
M
Seliger
B
B
Rodríguez-Peña
A
A
Bernal
J
J
Muñoz
A
A
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D018776:Genes, erbA; D051379:Mice; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000502:physiology
D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone