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Notch signaling is involved in expression of thyrocyte differentiation markers and is down-regulated in thyroid

E Ferretti1, E Tosi, A Po

  • 1Dipartimento di Scienze Cliniche, Università degli Studi di Roma La Sapienza, V.le del Policlinico, 155, 00161 Rome, Italy.

The Journal of Clinical Endocrinology and Metabolism
|July 31, 2008
PubMed
Abstract

Insights

Notch signaling regulates thyroid cell differentiation and growth. Its deregulation is linked to thyroid cancer, as restoring Notch-1 expression re-establishes differentiation and inhibits tumor growth.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Cell Signaling

Background:

  • Notch signaling pathways regulate cell growth and differentiation.
  • The role of Notch signaling in thyroid follicular cells is not fully understood.

Purpose of the Study:

  • To characterize Notch pathway component expression in thyroid follicular cells.
  • To investigate Notch signaling activity in normal and cancerous thyrocytes.

Main Methods:

  • Quantitative RT-PCR and immunohistochemistry on murine and human thyroid tissues.
  • Gene expression analysis, proliferation assays, and reporter gene assays in human thyroid cancer cells.

Main Results:

  • Notch receptor expression correlates with differentiation markers in murine thyrocytes and is TSH-regulated.
  • Notch component expression is reduced in undifferentiated human thyroid tumors.
  • Notch-1 overexpression in cancer cells restored differentiation, reduced proliferation, and increased NIS expression.

Conclusions:

  • Notch signaling is crucial for thyroid cell fate determination and regulates thyroid-specific gene expression.
  • Deregulation of Notch signaling may contribute to thyroid cancer dedifferentiation.

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