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Neuronal Properties of Thyroid C-Cell Tumor Lines

Chapter
Part of the Medical Intelligence Unit book series (MIU.LANDES)

Abstract

Thyroid C-cells present a paradoxical phenotype of neuronal properties in multiple endocrine neoplasia type 2 (MEN 2). The neuronal phenotype is in contrast to the primarily endocrine nature of the parental C-cells. What can account for this transdifferentiation? In this chapter, we will try to answer that question by comparing the neuronal features of C-cell lines with those of normal C-cells treated with nerve growth factor. From that perspective, we will then present a model proposing that ret tyrosine kinase activity is responsible for the neuronal properties in C-cell tumors. Interestingly, the neuronal phenotype is partly reversible. Overexpression of the ras oncogene or treatment with glucocorticoids inhibits both cell growth and induces a more endocrine state. An attractive hypothesis is that these agents might be decreasing ret activity, although this remains to be tested. The utility of thyroid C-cell lines for identification of differentiation and growth genes will be exemplified by description of a novel splice product of the Gsα transcript that is selectively expressed in a subset of neuroendocrine and neuronal cells. Finally, the applicability of C-cell lines for studying fundamental transcriptional control mechanisms will be described using the calcitonin/CGRP gene as a model. In summary, the induction and repression of neuronal properties in C-cell tumors provide a useful system for studying the genetic mechanisms underlying gene expression and differentiation in MEN 2.

Keywords

Nerve Growth Factor Neural Crest Medullary Thyroid Carcinoma Multiple Endocrine Neoplasia Type Neuronal Phenotype 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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