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