Document Detail


Thyroglobulin may affect telomerase activity in thyroid follicular cells.
MedLine Citation:
PMID:  18830915     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Telomerase (TA) activity is known to be present in malignant tumor cells, but not in most somatic differentiated cells. TA shows relatively high activity in thyroid cancer cells, but reports vary. This fact prompted us to elucidate whether cell component inhibitors of TA in the thyroid follicles can modulate its activity. The activity of TA extracted from Hela cells was inhibited by mixing with the supernatant fraction of human thyroid tissue extract. To examine the effect of iodine, thyroid hormones (l-T3 and l-T4) and human thyroglobulin (hTg) contained in the thyroid follicles, l-T3, l-T4 and hTg were added to the TRAP assay system in vitro, using TA from Hela cells. Iodine, l-T3 and l-T4 did not affect TA activity, but hTg inhibited the TA activity in a dose-dependent manner (IC(50) of hTg: ca 0.45 microM: inhibiting concentration of hTg was from 0.15 microM to 3.0 microM). The hTg inhibition was not evident in the RT-PCR system, suggesting no effect of hTg on Taq DNA polymerase activity. The hTg inhibition of TA activity was attenuated by dNTP but not significantly by TS primer. These data suggest that hTg contained in thyroid follicular cells of various thyroid diseases may affect the TA activity measured in biopsied thyroid specimens, and that the reduction of the TA activity by hTg may induce slow progression and growth, and low grade malignancy of thyroid cancer, particularly differentiated carcinoma.
Authors:
Akio Nagasaka; Naohisa Oda; Akira Nakai; Keiko Hotta; Mutsuko Nagata; Taiya Kato; Atsushi Suzuki; Mitsuyasu Itoh; Hitoshi Miura; Motoo Hakuta; Shonen Yoshida; Yatsuka Hibi; Katsumi Iwase
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of enzyme inhibition and medicinal chemistry     Volume:  24     ISSN:  1475-6374     ISO Abbreviation:  J Enzyme Inhib Med Chem     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-16     Completed Date:  2009-08-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101150203     Medline TA:  J Enzyme Inhib Med Chem     Country:  England    
Other Details:
Languages:  eng     Pagination:  524-30     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
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MeSH Terms
Descriptor/Qualifier:
Carcinoma, Papillary, Follicular / enzymology,  metabolism
Dose-Response Relationship, Drug
Hela Cells
Humans
Reverse Transcriptase Polymerase Chain Reaction
Telomerase / metabolism*
Thyroglobulin / pharmacology*
Thyroid Gland / enzymology*,  metabolism
Thyroid Neoplasms / enzymology,  metabolism
Time Factors
Chemical
Reg. No./Substance:
9010-34-8/Thyroglobulin; EC 2.7.7.49/Telomerase

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