Related Experiment Videos
c-erbA and v-erbA modulate growth and gene expression of a mouse glial precursor cell line
T Iglesias1, S Llanos, M López-Barahona
1Instituto de Investigaciones Biomédicas, CSIC, Madrid, Spain.
Abstract:
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)
Insights
Thyroid hormone receptor alpha 1 (TR alpha 1) expression inhibits glial cell proliferation, while the v-erbA oncogene enhances it. TR alpha 1 affects gene expression and growth factor responses differently than v-erbA.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- The c-erbA alpha protooncogene encodes the thyroid hormone receptor alpha 1 (TR alpha 1).
- The viral v-erbA oncogene is a mutated form of c-erbA alpha.
- Glial cell proliferation is influenced by various growth factors and hormones.
Purpose of the Study:
- To investigate the effects of TR alpha 1 and v-erbA expression on glial cell proliferation and gene expression.
- To compare the responses of glial cells expressing TR alpha 1 or v-erbA to growth factors and thyroid hormone.
Main Methods:
- Retroviral vectors were used to express c-erbA alpha and v-erbA in an immortal mouse glial cell line (B3.1).
- Cell proliferation was assessed under various serum conditions and in the presence of different growth factors (PDGF, bFGF, IGF-I) and thyroid hormone (T3).
- Gene expression of astrocytic (GFAP, vimentin) and oligodendrocytic (PDE) markers was analyzed.
Main Results:
- TR alpha 1 expression decreased cell proliferation, particularly in serum-free conditions, and altered responses to growth factors.
- v-erbA expression increased DNA synthesis and showed distinct responses to IGF-I, while inhibiting an oligodendrocytic marker.
- TR alpha 1 expression, in the presence of T3, downregulated astrocytic genes (GFAP, vimentin).
Conclusions:
- TR alpha 1 and v-erbA exert opposing effects on glial cell proliferation and differentiation.
- Thyroid hormone signaling through TR alpha 1 plays a role in regulating glial cell fate and gene expression.
- These findings have implications for understanding glial cell development and oncogenesis.