AJTR Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Am J Transl Res 2010;2(1):119-125

Review Article
Notch in the development of thyroid C-cells and the treatment of
medullary thyroid cancer

Mackenzie Cook, Xiao-Min Yu, Herbert Chen

Section of Endocrine Surgery, Department of Surgery, University of Wisconsin, Madison, Wisconsin

Received January 16, 2010; accepted February 2, 2010, available online February 10, 2010

Abstract: The Notch pathway plays an important role in the normal development of neuroendocrine cells,
including the calcitonin producing C-cells of the thyroid.  This effect has been elucidated to be mediated through
modulation of Achaete-Scute Complex Like 1 (ASCL1), a transcription factor associated with poor prognosis in
neuroendocrine cancer. Medullary thyroid cancer (MTC) is one of the neuroendocrine cancers derived from the
thyroid C-cells. The Notch pathway has been shown to be inactive in MTC which may lead to altered expression of
ASCL1.  Artificial induction of Notch signaling in MTC cells can suppress ASCL1 expression, the cell growth as
well as hormone secreting potential.  Pharmacological activation of the Notch pathway also successfully
suppresses the tumor growth in an animal model, which sheds light on the targeted therapy of Notch as a
potential treatment for intractable MTC. (AJTR1001003).

Key words: Notch, achaete-scute complex like 1, medullary thyroid cancer

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