Effects of 13 cis-retinoic acid on growth and differentiation of human follicular carcinoma cells (UCLA R0 82 W-1) in vitro.
Dedifferentiation of human thyroid tumors is frequently found in humans. The effect of retinoids (13 cis-RA) was studied on the proliferation and differentiation of a human follicular cell line in vitro (UCLA R0 82 W-1). A significant and dose-dependent reduction (P less than 0.001) in cell number and [3H] thymidine uptake was found in cells exposed to 13 cis-RA up to 10 microM. Higher concentrations of 13 cis-RA, however, led to a dose-dependent restoration of cell proliferation. Various parameters of differentiation increased under the influence of 13 cis-RA (10 microM) over nonexposed cells. The 125I uptake increased 4-fold over that in control nonexposed cells (P less than 0.05). [125I] Epidermal growth factor binding increased 5-fold, and [125I] human TSH binding increased significantly after exposure to 13 cis-RA (P less than 0.02). Deiodinase activity, however, was significantly lower in 13 cis-RA exposed cells than in control cells. The present study shows that 13 cis-RA (10 microM) drives the tumor cells toward a more normal state of proliferation and differentiation.
Department of Medicine, University of California School of Medicine, Los Angeles 90024.
A J
AJ
Van Herle
M L
ML
Agatep
D N
DN
Padua
T L
TL
Totanes
D V
DV
Canlapan
H M
HM
Van Herle
G J
GJ
Juillard
D000230:Adenocarcinoma / Q000378:metabolism; D001665:Binding Sites / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000378:metabolism; D007455:Iodine / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D014212:Tretinoin; D004815:Epidermal Growth Factor; D013972:Thyrotropin; D007455:Iodine; D007453:Iodide Peroxidase; D013936:Thymidine