J Korean Endocr Soc.  2009 Jun;24(2):93-99. 10.3803/jkes.2009.24.2.93.

Search for Materials that Influence Human Medullary Thyroid Carcinoma Cell Proliferation

• Shin HW
• Jang HW
• Kim KS
• Lee JI
• Park JY
• Kim SW
• Min YK
• Lee MS
• Lee MK
• Kim KW
• Chung JH

• KMID: 1468503
• DOI: http://doi.org/10.3803/jkes.2009.24.2.93

Abstract

BACKGROUND: Surgical excision is the only effective treatment of medullary thyroid carcinoma (MTC) and there is no certain treatment for recurrence or distant metastasis. Materials that influence MTC cell proliferation were recently reported. Presently, we evaluated the influence of dexamethasone, somatostatin, progesterone, estradiol-17-beta, forskolin and gastrin on MTC cell proliferation and calcitonin secretion.
METHODS
Genomic DNA was extracted and sequenced from untreated thyroid TT cells and cells treated with 10-5~10-10 M dexamethasone, somatostatin, progesterone, estradiol-17-beta, forskolin or gastrin, and cultured for 1~6 days. Cell proliferation was assessed using a BrdU assay at days 1, 2, 3, and 6. Calcitonin in the culture medium from dexamethasone-treated TT cells was measured at days 1~3.
RESULTS
Replacement of cysteine with tryptophan at codon 634 of exon 11 was evident in treated TT cells. There was no significant difference in cell proliferation at days 1~3 in cells treated with somatostatin, progesterone, estradiol-17-beta, gastrin and forskolin, while proliferation was inhibited in dexamethasone-treated cells in a concentration-dependent manner from 10-5~10-8 M with no inhibition evident at 10-10 M. Calcitonin levels in 10-5~10-8 M dexamethasone-treated cells were decreased.
CONCLUSION
Dexamethasone is a potentially useful compound to suppress MTC cell proliferation. Further studies are necessary to explore this potential further prior to clinical use.

Keyword

calcitonin; dexamethasone; estradiol-17-beta; forskolin; gastrin; medullary thyroid carcinoma; progesterone; somatostatin

MeSH Terms

Bromodeoxyuridine
Calcitonin
Cell Proliferation
Codon
Cysteine
Dexamethasone
DNA
Exons
Forskolin
Gastrins
Humans
Neoplasm Metastasis
Progesterone
Recurrence
Somatostatin
Thyroid Gland
Thyroid Neoplasms
Tryptophan
Bromodeoxyuridine
Calcitonin
Codon
Cysteine
DNA
Dexamethasone
Forskolin
Gastrins
Progesterone
Somatostatin
Tryptophan

Figure

• 

  Fig. 1. Direct sequence analysis of RET mutation in TT cells. The substitution of Cys (TGC) to Trp (TGG) was detected at codon 634 of exon 11.

• 

  Fig. 2. Time and dose related effects of dexamethasone (A) progesterone (B) estradiol-17-beta (C) gastrin (D) somatostatin (E) and forskolin (F) on TT cell proliferation. The dose dependent decrease in TT cell proliferation with exposure to only dexamethasone is demonstrated. Results presented are the mean of proliferation ratio (mean ±SD).

• 

  Fig. 3. Calcitonin levels during TT cell proliferation. Calcitonin levels are increased steadily at the control during 1, 2, 3 day. Calcitonin levels in the dexamethasone treated cells (10-8, 10-6 10-5 M) are inhibited about the increase in Calcitonin levels (* P < 0.05 vs. control day 1, †P < 0.05 vs. control day 2). Results presented are the mean of Calcitonin levels (mean ±SD).

Reference

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