In-vivo activation of Raf-1 inhibits tumor growth and development in a xenograft model of human medullary thyroid cancer

Academic Article


  • Apart from surgical resection, there are no effective therapies for medullary thyroid cancer, a neuroendocrine tumor derived from parafollicular C cells. We have previously shown that activation of raf-1 in TT-raf cells by estradiol suppresses tumor cell growth and calcitonin secretion in vitro. TT-raf cells are a human medullary thyroid cancer cell line that contains an estrogen-inducible raf-1 construct. The in-vivo effects of raf-1 activation in this cell line, however, have not been characterized. Therefore, we utilized TT or TT-raf cells in a murine subcutaneous xenograft model to study tumor development and growth. Activation of raf-1, in mice with TT-raf tumors, led to a significant decrease in medullary thyroid cancer tumor formation. Control groups, however, had a high rate of medullary thyroid cancer tumor development. These data indicate that raf-1 activation by estradiol treatment in this TT-raf xenograft model inhibited tumor development. Furthermore, to determine whether raf-1 activation could also inhibit the growth of established tumors, estradiol and control pellets were implanted after tumor development. The TT-raf group that received estradiol pellets showed an 8-fold decrease in tumor volume compared with the TT-raf control group. Taken together, these results suggest that in-vivo activation of raf-1 in a murine model of medullary thyroid cancer not only led to a reduction in tumor development, but also inhibited the growth of established tumors. These results suggest that strategies to activate the raf-1/MEK/ERK1/2 signaling pathway may be a viable approach to treat patients with metastatic medullary thyroid cancer. © 2006 Lippincott Williams & Wilkins.
  • Published In

  • Anti-Cancer Drugs  Journal
  • Digital Object Identifier (doi)

    Author List

  • Vaccaro A; Chen H; Kunnimalaiyaan M
  • Start Page

  • 849
  • End Page

  • 853
  • Volume

  • 17
  • Issue

  • 7