Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma

A. de Bustros, S. B. Baylin, C. L. Berger, B. A. Roos, S. S. Leong, B. D. Nelkin

Research output: Contribution to journalArticle

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Abstract

Medullary thyroid carcinoma is a tumor of the calcitonin-secreting thyroid C-cell, with a variable malignant potential. Virulent tumors are characterized by decreased calcitonin production, suggesting the emergence of a less differentiated medullary thyroid carcinoma cell. In order to further delineate relationships between tumor progression and status of differentiation of medullary thyroid carcinoma cells, we have sought to chemically manipulate the TT cell line, an established culture of human medullary thyroid carcinoma, derived from a patient with aggressive disease. We found that the phorbol esters, 12-O-tetradecanoyl phorbol 13-acetate and phorbol 12,13-dibutyrate 1) altered the morphology of the TT cells towards that of high-calcitonin-containing cells; 2) enhanced calcitonin secretion 7-fold; 3) increased calcitonin production at the transcriptional level by 2-fold; 4) inhibited cellular proliferation; and 5) decreased, by 80%, the levels of the c-myc gene mRNA. These data suggest that phorbol ester induce, in human medullary thyroid carcinoma cells in culture, a programmed pattern of events resulting in differentiation of these cells.

Original languageEnglish
Pages (from-to)98-104
Number of pages7
JournalJournal of Biological Chemistry
Volume260
Issue number1
StatePublished - Apr 10 1985
Externally publishedYes

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Calcitonin
Phorbol Esters
Transcription
Genes
Cells
Messenger RNA
Tumors
Cell culture
Phorbol 12,13-Dibutyrate
Neoplasms
myc Genes
Tetradecanoylphorbol Acetate
Cell Differentiation
Thyroid Gland
Cell Culture Techniques
Cell Proliferation
Medullary Thyroid cancer
Cell Line

ASJC Scopus subject areas

  • Biochemistry

Cite this

de Bustros, A., Baylin, S. B., Berger, C. L., Roos, B. A., Leong, S. S., & Nelkin, B. D. (1985). Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma. Journal of Biological Chemistry, 260(1), 98-104.

Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma. / de Bustros, A.; Baylin, S. B.; Berger, C. L.; Roos, B. A.; Leong, S. S.; Nelkin, B. D.

In: Journal of Biological Chemistry, Vol. 260, No. 1, 10.04.1985, p. 98-104.

Research output: Contribution to journalArticle

de Bustros, A, Baylin, SB, Berger, CL, Roos, BA, Leong, SS & Nelkin, BD 1985, 'Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma', Journal of Biological Chemistry, vol. 260, no. 1, pp. 98-104.
de Bustros, A. ; Baylin, S. B. ; Berger, C. L. ; Roos, B. A. ; Leong, S. S. ; Nelkin, B. D. / Phorbol esters increase calcitonin gene transcription and decrease c-myc mRNA levels in cultured human medullary thyroid carcinoma. In: Journal of Biological Chemistry. 1985 ; Vol. 260, No. 1. pp. 98-104.
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