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

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127 引文 斯高帕斯(Scopus)


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.
頁(從 - 到)180-187
出版狀態已發佈 - 2月 2007

ASJC Scopus subject areas

  • 生物化學
  • 分子生物學
  • 內分泌
  • 藥理
  • 臨床生物化學
  • 有機化學


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