Actin stress fiber disruption and tropomyosin isoform switching in normal thyroid epithelial cells stimulated by thyrotropin and phorbol esters.
Thyrotropin (TSH), through cyclic AMP, promotes both proliferation and differentiation expression in dog thyroid epithelial cells in primary culture, whereas the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulates proliferation but antagonizes differentiating effects of TSH. In this study, within 20 min both factors triggered the disruption of actin-containing stress fibers. This process preceded distinct morphological changes: cytoplasmic retraction and arborization in response to TSH and cyclic AMP, cell shape distortion, and increased motility in response to TPA and cyclic AMP, cell shape distortion, and increased motility in response to TPA and diacylglycerol. TSH and TPA also induced a marked decrease in the synthesis of three high Mr tropomyosin isoforms, which were not present in dog thyroid tissue but appeared in culture during cell spreading and stress fiber formation. In contrast, the synthesis of two low Mr forms of tropomyosin that were already present in thyroid tissue remained unchanged after treatment with TSH or TPA. Epidermal growth factor, another mitogenic and dedifferentiating factor for these cells, did not induce acute morphological changes, nor modification of tropomyosin synthesis. The tropomyosin isoform switching observed here closely resembled similar processes in various cells transformed by oncogenic viruses. However, it did not correlate with differentiation or mitogenic activation. Contrasting with current hypothesis on this process in transformed cells, tropomyosin isoform switching in normal thyroid cells was preceded and thus might be caused by early disruption of stress fibers.
Roger
P P
PP
Institute of Interdisciplinary Research, School of Medicine, Free University of Brussels, Belgium.
Rickaert
F
F
Lamy
F
F
Authelet
M
M
Dumont
J E
JE
D008841:Actin Cytoskeleton / Q000648:ultrastructure*; D000199:Actins / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology; D003599:Cytoskeleton / Q000648:ultrastructure*; D004285:Dogs; D015180:Electrophoresis, Gel, Two-Dimensional; D004848:Epithelium / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D007526:Isoelectric Point; D008970:Molecular Weight; D011493:Protein Kinase C / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013961:Thyroid Gland / Q000648:ultrastructure*; D013972:Thyrotropin / Q000494:pharmacology*; D014335:Tropomyosin / Q000502:physiology*
D000199:Actins; D014335:Tropomyosin; D013972:Thyrotropin; D000242:Cyclic AMP; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate