Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic

Hung Yun Lin, Heng Yuan Tang, Ai Shih, Travis Keating, Gary Cao, Paul J. Davis, Faith B. Davis

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Thyroid hormone (l-thyroxine, T 4, or 3,5,3′-triiodo-l-thyronine, T 3) treatment of human papillary and follicular thyroid cancer cell lines resulted in enhanced cell proliferation, measured by proliferating cell nuclear antigen (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK1/2) signal transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid (tetrac), that inhibits binding of iodothyronines to the cell surface receptor for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD 98059, also blocked hormone-induced cell proliferation. We then assessed the possibility that thyroid hormone is anti-apoptotic. We first established that resveratrol (10 μM), a pro-apoptotic agent in other cancer cells, induced p53-dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary and follicular thyroid cancer cells. Induction of apoptosis by the stilbene required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and apoptosis were inhibited more than 50% by physiological concentrations of T 4. T 4 activated MAPK in the absence of resveratrol, caused minimal Ser-15 phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance. Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone promotes papillary and follicular thyroid cancer cell proliferation in vitro.

Original languageEnglish
Pages (from-to)180-187
Number of pages8
JournalSteroids
Volume72
Issue number2
DOIs
Publication statusPublished - Feb 2007
Externally publishedYes

Fingerprint

Thyroid Hormones
Thyroid Neoplasms
Intercellular Signaling Peptides and Proteins
Cells
Cell proliferation
Cell Proliferation
Phosphorylation
Chemical activation
Apoptosis
Gene expression
Integrin alphaVbeta3
jun Genes
Thyronines
Gene Expression
Stilbenes
Signal transduction
Mitogen-Activated Protein Kinase Kinases
Proliferating Cell Nuclear Antigen
Cell Surface Receptors
Cell membranes

Keywords

  • Mitogen-activated protein kinase
  • Resveratrol
  • Tetraiodothyroacetic acid
  • Thyroid cancer
  • Thyroxine

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic. / Lin, Hung Yun; Tang, Heng Yuan; Shih, Ai; Keating, Travis; Cao, Gary; Davis, Paul J.; Davis, Faith B.

In: Steroids, Vol. 72, No. 2, 02.2007, p. 180-187.

Research output: Contribution to journalArticle

Lin, Hung Yun ; Tang, Heng Yuan ; Shih, Ai ; Keating, Travis ; Cao, Gary ; Davis, Paul J. ; Davis, Faith B. / Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic. In: Steroids. 2007 ; Vol. 72, No. 2. pp. 180-187.
@article{4dc2bd788dfd49248f9f0a12c9a9c91a,
title = "Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic",
abstract = "Thyroid hormone (l-thyroxine, T 4, or 3,5,3′-triiodo-l-thyronine, T 3) treatment of human papillary and follicular thyroid cancer cell lines resulted in enhanced cell proliferation, measured by proliferating cell nuclear antigen (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK1/2) signal transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid (tetrac), that inhibits binding of iodothyronines to the cell surface receptor for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD 98059, also blocked hormone-induced cell proliferation. We then assessed the possibility that thyroid hormone is anti-apoptotic. We first established that resveratrol (10 μM), a pro-apoptotic agent in other cancer cells, induced p53-dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary and follicular thyroid cancer cells. Induction of apoptosis by the stilbene required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and apoptosis were inhibited more than 50{\%} by physiological concentrations of T 4. T 4 activated MAPK in the absence of resveratrol, caused minimal Ser-15 phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance. Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone promotes papillary and follicular thyroid cancer cell proliferation in vitro.",
keywords = "Mitogen-activated protein kinase, Resveratrol, Tetraiodothyroacetic acid, Thyroid cancer, Thyroxine",
author = "Lin, {Hung Yun} and Tang, {Heng Yuan} and Ai Shih and Travis Keating and Gary Cao and Davis, {Paul J.} and Davis, {Faith B.}",
year = "2007",
month = "2",
doi = "10.1016/j.steroids.2006.11.014",
language = "English",
volume = "72",
pages = "180--187",
journal = "Steroids",
issn = "0039-128X",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Thyroid hormone is a MAPK-dependent growth factor for thyroid cancer cells and is anti-apoptotic

AU - Lin, Hung Yun

AU - Tang, Heng Yuan

AU - Shih, Ai

AU - Keating, Travis

AU - Cao, Gary

AU - Davis, Paul J.

AU - Davis, Faith B.

PY - 2007/2

Y1 - 2007/2

N2 - Thyroid hormone (l-thyroxine, T 4, or 3,5,3′-triiodo-l-thyronine, T 3) treatment of human papillary and follicular thyroid cancer cell lines resulted in enhanced cell proliferation, measured by proliferating cell nuclear antigen (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK1/2) signal transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid (tetrac), that inhibits binding of iodothyronines to the cell surface receptor for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD 98059, also blocked hormone-induced cell proliferation. We then assessed the possibility that thyroid hormone is anti-apoptotic. We first established that resveratrol (10 μM), a pro-apoptotic agent in other cancer cells, induced p53-dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary and follicular thyroid cancer cells. Induction of apoptosis by the stilbene required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and apoptosis were inhibited more than 50% by physiological concentrations of T 4. T 4 activated MAPK in the absence of resveratrol, caused minimal Ser-15 phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance. Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone promotes papillary and follicular thyroid cancer cell proliferation in vitro.

AB - Thyroid hormone (l-thyroxine, T 4, or 3,5,3′-triiodo-l-thyronine, T 3) treatment of human papillary and follicular thyroid cancer cell lines resulted in enhanced cell proliferation, measured by proliferating cell nuclear antigen (PCNA). Thyroid hormone also induced activation of the Ras/MAPK (ERK1/2) signal transduction pathway. ERK1/2 activation and cell proliferation caused by thyroid hormone were blocked by an iodothyronine analogue, tetraiodothyroacetic acid (tetrac), that inhibits binding of iodothyronines to the cell surface receptor for thyroid hormone on integrin alphaVbeta3. A MAPK cascade inhibitor at MEK, PD 98059, also blocked hormone-induced cell proliferation. We then assessed the possibility that thyroid hormone is anti-apoptotic. We first established that resveratrol (10 μM), a pro-apoptotic agent in other cancer cells, induced p53-dependent apoptosis and c-fos, c-jun and p21 gene expression in both papillary and follicular thyroid cancer cells. Induction of apoptosis by the stilbene required Ser-15 phosphorylation of p53. Resveratrol-induced gene expression and apoptosis were inhibited more than 50% by physiological concentrations of T 4. T 4 activated MAPK in the absence of resveratrol, caused minimal Ser-15 phosphorylation of p53 and did not affect c-fos, c-jun and p21 mRNA abundance. Thus, plasma membrane-initiated activation of the MAPK cascade by thyroid hormone promotes papillary and follicular thyroid cancer cell proliferation in vitro.

KW - Mitogen-activated protein kinase

KW - Resveratrol

KW - Tetraiodothyroacetic acid

KW - Thyroid cancer

KW - Thyroxine

UR - http://www.scopus.com/inward/record.url?scp=33847060499&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847060499&partnerID=8YFLogxK

U2 - 10.1016/j.steroids.2006.11.014

DO - 10.1016/j.steroids.2006.11.014

M3 - Article

VL - 72

SP - 180

EP - 187

JO - Steroids

JF - Steroids

SN - 0039-128X

IS - 2

ER -