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Medullary Thyroid Carcinoma pp 1–39Cite as

Thyroid C-Cell Biology and Oncogenic Transformation

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Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 204))

Abstract

The thyroid parafollicular cell, or commonly named “C-cell,” functions in serum calcium homeostasis. Elevations in serum calcium trigger release of calcitonin from the C-cell, which in turn functions to inhibit absorption of calcium by the intestine, resorption of bone by the osteoclast, and reabsorption of calcium by renal tubular cells. Oncogenic transformation of the thyroid C-cell is thought to progress through a hyperplastic process prior to malignancy with increasing levels of serum calcitonin serving as a biomarker for tumor burden. The discovery that multiple endocrine neoplasia type 2 is caused by activating mutations of the RET gene serves to highlight the RET-RAS-MAPK signaling pathway in both initiation and progression of medullary thyroid carcinoma (MTC). Thyroid C-cells are known to express RET at high levels relative to most cell types; therefore, aberrant activation of this receptor is targeted primarily to the C-cell, providing one possible cause of tissue-specific oncogenesis. The role of RET signaling in normal C-cell function is unknown though calcitonin gene transcription appears to be sensitive to RET activation. Beyond RET, the modeling of oncogenesis in animals and screening of human tumors for candidate gene mutations have uncovered mutation of RAS family members and inactivation of Rb1 regulatory pathway as potential mediators of C-cell transformation. A growing understanding of how RET interacts with these pathways, both in normal C-cell function and during oncogenic transformation, will help in the development of novel molecular-targeted therapies.

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Acknowledgments

G.J. Cote is supported by NIH/NCI grant P50 CA168505.

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  1. Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1461, Houston, TX, 77030, USA

    Gilbert J. Cote & Marie-Claude Hofmann

  2. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1484, Houston, TX, 77030, USA

    Elizabeth G. Grubbs

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  1. Gilbert J. Cote
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Correspondence to Gilbert J. Cote .

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  1. Endocrine Practice and Molecular Laboratory, Medical Faculty, University of Heidelberg , Heidelberg, Germany

    Friedhelm Raue

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Cote, G.J., Grubbs, E.G., Hofmann, MC. (2015). Thyroid C-Cell Biology and Oncogenic Transformation. In: Raue, F. (eds) Medullary Thyroid Carcinoma. Recent Results in Cancer Research, vol 204. Springer, Cham. https://doi.org/10.1007/978-3-319-22542-5_1

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