c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line.
The c-erbA alpha protooncogene coding for the thyroid hormone (T3) receptor (TR alpha 1) and the viral, mutated v-erbA oncogene were expressed in an immortal mouse glial cell line (B3.1) using retroviral vectors. c-erbA alpha expression led to a decrease in cell proliferation in high and low serum conditions, both in the presence and in the absence of T3. In serum-free medium, c-erbA-expressing cells (B3.1 + TR alpha 1) were completely arrested, whereas cells expressing v-erbA (B3.1 + v-erbA) showed a higher DNA synthesis rate than normal B3.1 cells. Although proliferation of all three cell types was stimulated by platelet-derived growth factor and basic fibroblast growth factor, differences were also observed in the response to these agents. B3.1 + TR alpha 1 cells were more sensitive to platelet-derived growth factor than B3.1 and B3.1 + v-erbA cells. In contrast, B3.1 cells responded to basic fibroblast growth factor better than B3.1 + TR alpha 1 or B3.1 + v-erbA cells. Insulin-like growth factor I potentiated the action of platelet-derived growth factor and basic fibroblast growth factor. Again, different responses to treatment with insulin-like growth factor I alone were observed; B3.1 + TR alpha 1 cells did not respond to it, whereas B3.1 + v-erbA cells showed a dramatic stimulation by this agent. Interestingly, in the presence of T3, the blockade in B3.1 + TR alpha 1 cell proliferation was accompanied by the down-regulation of the typical astrocytic genes, glial fibrillary acidic protein and vimentin. These hormone effects were not found in v-erbA-expressing cells. In addition, v-erbA inhibited the basal expression of the cyclic nucleotide phosphodiesterase gene, an oligodendrocytic marker.(ABSTRACT TRUNCATED AT 250 WORDS)
Iglesias
T
T
Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
Llanos
S
S
López-Barahona
M
M
Pérez-Aranda
A
A
Rodríguez-Peña
A
A
Bernal
J
J
Höhne
A
A
Seliger
B
B
Muñoz
A
A
D000818:Animals; D015415:Biomarkers; D001921:Brain / Q000166:cytology / Q000196:embryology; D002455:Cell Division; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology*; D018774:Oncogene Proteins v-erbA / Q000235:genetics / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014284:Triiodothyronine / Q000494:pharmacology
D015415:Biomarkers; D007328:Insulin; D018774:Oncogene Proteins v-erbA; D010982:Platelet-Derived Growth Factor; D011988:Receptors, Thyroid Hormone; D011993:Recombinant Fusion Proteins; D014284:Triiodothyronine; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I