Decreased growth rate and tumour formation of human anaplastic thyroid carcinoma cells transfected with a human thyrotropin receptor cDNA in NMRI nude mice treated with propylthiouracil.
The effect of the human TSH-receptor (TSHR) on the growth of human anaplastic thyroid carcinoma cells lacking the endogenous expression of TSHR, was studied both in vitro and in vivo in NMRI nude mice. Cells from a human anaplastic thyroid carcinoma cell line (C643) were transfected with a TSHR cDNA, and clones were isolated after neomycin selection. The expression of a functional receptor protein was ensured by analysis of the specific binding of 125I-TSH and measurement of TSH-induced cAMP. Incorporation of [3H]thymidine and increase in cell number was slightly inhibited by TSH in TSHR-expressing cells in vitro. In order to investigate whether the regained expression of a functional TSHR protein in C643 cells could influence the in vivo growth, cells were injected subcutaneously into NMRI nude mice. To manipulate the endogenous level of TSH, animals were given 6n-propyl-2-thiouracil (PTU; resulting in a high TSH level), T4 (a low TSH level) or no treatment (as a control). There seemed to be a TSH induced inhibition of tumour growth, since tumours in mice treated with PTU grew after a longer take rate and with a slower growth rate. The present results suggest a TSH-mediated growth inhibition in the TSHR-transfected C 643 anaplastic thyroid carcinoma cells.
Department of Pathology, University Hospital, Uppsala, Sweden.
B
B
Gustavsson
A
A
Hermansson
A C
AC
Andersson
L
L
Grimelius
J
J
Bergh
B
B
Westermark
N E
NE
Heldin
D000818:Animals; D013956:Antithyroid Agents / Q000008:administration & dosage*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D002455:Cell Division / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D011441:Propylthiouracil / Q000008:administration & dosage*; D011989:Receptors, Thyrotropin / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D013956:Antithyroid Agents; D018076:DNA, Complementary; D011989:Receptors, Thyrotropin; D011441:Propylthiouracil