Endocrine Differentiation and the Role of Notch1

Funding:

American Cancer Society

Principal Investigator:

Herbert Chen, MD

Lab Website:

Dr. Chen's Lab

Project Summary:

Background: Neuroendocrine (NE) tumors such as carcinoid, islet cell tumors, and medullary thyroid cancer are the second most common cause of isolated hepatic metastases, and often cause debilitating symptoms due to excessive hormonal secretion. Besides surgery, there are limited curative and palliative treatments available to patients with NE tumors, emphasizing the need for development of other forms of therapy.

Objective/Hypothesis: We have recently shown that induction of Notch1 in human carcinoid and medullary thyroid cancer cells markedly suppresses tumor cell growth and NE hormone production. In this proposal, we will determine which components of the Notch1 pathway play essential roles in mediating this significant biological and potentially therapeutic effect in NE tumor cells.

Specific Aims: (1) To delineate the downstream effectors of Notch1 signaling in NE tumor cells; (2) To delineate the mechanism of Notch1-mediated hormone suppression in NE tumor cells; and (3) To determine if activation of Notch1 affects NE tumor progression and hormone production in vivo.

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First published: 07/15/02 Last updated: 05/17/08 webmaster@surgery.wisc.edu
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