In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 3923-3923
Abstract:
Neuroendocrine tumors are rare forms of cancers originating from hormone-producing cells that are scattered throughout the body. Medullary thyroid carcinoma (MTC) develops from calcitonin-secreting, C cells, in the thyroid gland. Surgical removal of the thyroid is the best treatment currently available for early stage cancer patients but advanced forms of MTC are often incurable and fatal. Thus, better therapies are needed. A lack of relevant animal models for this disease has slowed the development of new treatments. We have recently reported a novel conditional mouse model for MTC. In these mice, overexpression of the cyclin-dependent kinase 5 (Cdk 5), activator, p25 in C cells induces MTC tumors. Furthermore, interruption of p25 overexpression results in growth arrest of these tumors. Here we take advantage of our conditional mouse model to investigate the molecular pathways underlying MTC tumorigenesis. We used Illumina Mouse WG-6 v2.0 Expression BeadChip to compare the gene expression profile of proliferating versus arrested mouse MTC tumors. We found that a total of 920 genes encoding transcription factors, cell cycle proteins, motor proteins and angiogenesis factors were differentially regulated in growing versus arrested tumors. Particularly the genes encoding cell cycle proteins that are involved in the regulation of Rb pathway were significantly up-regulated in the proliferating tumors. Selected genes with higher degrees of change were evaluated by quantitative PCR and immunoblotting analyses. Taken together these findings suggests that the Rb signaling pathways is involved in MTC tumorigenesis and that Cdk5 may act as a critical regulator of the Rb signaling pathway in this cancer. Thus, targeting Cdk5 and/or the Rb pathway may be a valid strategy to stop the progression of neuroendocrine thyroid cancer. Citation Format: Karine Pozo, Antje Hillmann, Alexander Augustyn, Tanvir Singh, Florian Plattner, John Minna, Herbert Chen, Gilbert J. Cote, James A. Bibb, Fiemu E. Nwariaku. Molecular characterization of an animal model for neuroendocrine thyroid cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3923. doi:10.1158/1538-7445.AM2014-3923
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-3923
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
Permalink