Faculty Collaboration Database

Defective thyrotropin receptor G-protein cyclic adenosine monophosphate signaling mechanism in the FTC human follicular thyroid cancer cell line. Surgery 1997 Dec;122(6):1195-201; discussion 1201-2

Date

01/14/1998

Pubmed ID

9426438

DOI

10.1016/s0039-6060(97)90227-0

Scopus ID

2-s2.0-0031445135 (requires institutional sign-in at Scopus site)   8 Citations

Abstract

BACKGROUND: Several studies report the effect of thyrotropin (thyroid-stimulating hormone [TSH]) on FTC-133) and aggressively invasive (FTC-238) clones of a human follicular thyroid cancer cell line. Specifically, TSH induces fibronectin secretion by FTC-133, possibly as a result of increased cyclic adenosine monophosphate (cAMP), yet induces in vitro invasion through a protein kinase C-dependent mechanism. In normal thyrocytes, TSH activates cAMP through a stimulatory G-protein (Gs)-linked pathway. In the FTC model we studied the effect of TSH on adenylate cyclase activation.

METHODS: TSH receptor (TSH-R) mRNA was studied by reverse transcriptase polymerase chain reaction. Fibronectin transcription was analyzed by Northern blot and densitometry. cAMP levels were determined by an enzyme immunoassay. Gs alpha expression was determined by Western blot and a possible activating mutation at position 201 in Gs alpha sought by direct sequencing.

RESULTS: Reverse transcriptase polymerase chain reaction confirmed the presence of TSH-R mRNA in FTC-133 and FTC-238. TSH did not increase transcription of fibronectin mRNA. FTC-133 cells exhibited higher cAMP levels than did FTC-238 cells: 30.4 +/- 8.0 versus 13.0 +/- 3.5 femtomoles/10(4) cells (mean +/- SD; p < 0.001, Mann-Whitney rank-sum test). TSH did not raise cAMP levels in either clone. Gs alpha expression is equal in both cell lines and is not increased by TSH; sequencing showed no position 201 mutations in Gs alpha.

CONCLUSIONS: Prototypical TSH-Gs-cAMP signal transduction is not functional in FTC-133 or FTC-238. Our findings implicate perturbation in TSH-R.

Author List

Demeure MJ, Doffek KM, Wilson SD

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma, Follicular
Cyclic AMP
Fibronectins
GTP-Binding Proteins
Humans
RNA, Messenger
Receptors, Thyrotropin
Thyroid Neoplasms
Thyrotropin
Tumor Cells, Cultured