Thyroglobulin may affect telomerase activity in thyroid follicular cells.
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.
Nagasaka
Akio
A
Department of Internal Medicine, Fujita Health University School of Medicine, Toyoake, Aichi, Japan.
Oda
Naohisa
N
Nakai
Akira
A
Hotta
Keiko
K
Nagata
Mutsuko
M
Kato
Taiya
T
Suzuki
Atsushi
A
Itoh
Mitsuyasu
M
Miura
Hitoshi
H
Hakuta
Motoo
M
Yoshida
Shonen
S
Hibi
Yatsuka
Y
Iwase
Katsumi
K
D018265:Carcinoma, Papillary, Follicular / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000378:metabolism*; D013954:Thyroglobulin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000201:enzymology* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism; D013997:Time Factors
D013954:Thyroglobulin; D019098:Telomerase