Thyroglobulin may affect telomerase activity in thyroid follicular cells

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

Research output: Contribution to journalArticle

Abstract

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 (IC50 of hTg: ca 0.45 μM: inhibiting concentration of hTg was from 0.15 μM to 3.0 μM). 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.

Original languageEnglish
Pages (from-to)524-530
Number of pages7
JournalJournal of Enzyme Inhibition and Medicinal Chemistry
Volume24
Issue number2
DOIs
Publication statusPublished - 01-04-2009

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Thyroglobulin
Telomerase
Thyroid Gland
HeLa Cells
Thyroid Neoplasms
Human Activities
Iodine
Thyroid Epithelial Cells
Taq Polymerase
Tissue Extracts
Thyroid Diseases
Triiodothyronine
Cellular Structures
Thyroxine
Inhibitory Concentration 50
Neoplasms
Carcinoma
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery

Cite this

Nagasaka, Akio ; Oda, Naohisa ; Nakai, Akira ; Hotta, Keiko ; Nagata, Mutsuko ; Kato, Taiya ; Suzuki, Atsushi ; Itoh, Mitsuyasu ; Miura, Hitoshi ; Hakuta, Motoo ; Yoshida, Shonen ; Hibi, Yatsuka ; Iwase, Katsumi. / Thyroglobulin may affect telomerase activity in thyroid follicular cells. In: Journal of Enzyme Inhibition and Medicinal Chemistry. 2009 ; Vol. 24, No. 2. pp. 524-530.
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Nagasaka, A, Oda, N, Nakai, A, Hotta, K, Nagata, M, Kato, T, Suzuki, A, Itoh, M, Miura, H, Hakuta, M, Yoshida, S, Hibi, Y & Iwase, K 2009, 'Thyroglobulin may affect telomerase activity in thyroid follicular cells', Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 24, no. 2, pp. 524-530. https://doi.org/10.1080/14756360802218920

Thyroglobulin may affect telomerase activity in thyroid follicular cells. / Nagasaka, Akio; Oda, Naohisa; Nakai, Akira; Hotta, Keiko; Nagata, Mutsuko; Kato, Taiya; Suzuki, Atsushi; Itoh, Mitsuyasu; Miura, Hitoshi; Hakuta, Motoo; Yoshida, Shonen; Hibi, Yatsuka; Iwase, Katsumi.

In: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol. 24, No. 2, 01.04.2009, p. 524-530.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Thyroglobulin may affect telomerase activity in thyroid follicular cells

AU - Nagasaka, Akio

AU - Oda, Naohisa

AU - Nakai, Akira

AU - Hotta, Keiko

AU - Nagata, Mutsuko

AU - Kato, Taiya

AU - Suzuki, Atsushi

AU - Itoh, Mitsuyasu

AU - Miura, Hitoshi

AU - Hakuta, Motoo

AU - Yoshida, Shonen

AU - Hibi, Yatsuka

AU - Iwase, Katsumi

PY - 2009/4/1

Y1 - 2009/4/1

N2 - 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 (IC50 of hTg: ca 0.45 μM: inhibiting concentration of hTg was from 0.15 μM to 3.0 μM). 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.

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