A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis.

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Research Abstract Details 

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A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Abstract Text:

Viktor Johanson, Ahlman,Peter Bernhardt,Svante Jansson,Lars ,Fredrik Persson, Stenman,Christina ,Bo ,Mats Stridsberg,Ola Nilsson,

Hereditary medullary thyroid carcinoma (MTC) is caused by germline mutations in the RET proto-oncogene, resulting in constitutive activation of the RET tyrosine kinase. A substantial proportion of sporadic MTCs also have RET mutations, making the RET tyrosine kinase a potential therapeutic target in MTC. We have established a transplantable MTC in nude mice from a sporadic human MTC carrying a RET C634R mutation. Transplanted tumors had an exponential growth rate with an approximate doubling time of about 3 weeks, and expressed a neuroendocrine phenotype characteristic of MTC, e.g., expression of calcitonin, chromogranin A (CgA), synaptophysin, synaptic vesicle protein 2 (SV2), vesicular monoamine transporter-1 and -2, carcinoembryonic antigen, cytokeratin 8/18, epithelial cadherin, and neural cell adhesion molecule. Plasma calcitonin and CgA levels were elevated in tumor-bearing mice and correlated with tumor size. Cytogenetic analysis, including spectral karyotyping, confirmed the human origin of the xenografted tumors and demonstrated an abnormal, near triploid karyotype. Treatment of tumor-bearing nude mice with the tyrosine kinase inhibitor ZD6474, which specifically inhibits RET, epidermal growth factor receptor (EGFR), and vascular endothelium growth factor receptor (VEGFR) tyrosine kinases, resulted in a dose-dependent inhibition of tumor growth. Oral ZD6474 given once daily (250 mg/kg, 5 days/week) reduced tumor volume to 11% when compared with controls after 4 weeks. Our results show that this transplantable MTC, designated GOT2, represents a novel and useful model for studies of MTC and RET tyrosine kinase-dependent tumor growth.

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Publishing Authors By Initials

V Johanson,H Ahlman,P Bernhardt,S Jansson,L ,F Persson,G Stenman,C ,B ,M Stridsberg,O Nilsson,

For similar xenograft model antitumor assays research abstracts see: xenograft model antitumor assays research

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A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Endocrine-related cancer

VOLUME: 14

Page Numbers: 433-44

Journal Abbreviation: Endocr. Relat. Cancer

ISSN: 1351-0088

DAY: 20

MONTH: Jun

YEAR: 2007

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Information

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LANGUAGE: eng

NlmUniqueID: 9436481

A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Keywords Mesh Terms:

KEYWORDS: Xenograft Model Antitumor Assays

MESH TERMS: antagonists & inhibitors

Chemical & Substance for Abstract: A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis. Information

Substance Name: Vascular Endothelial Growth Factor Recep

Registry Number: EC 2.7.1.112

Grant and Affiliation Information for A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis.

AFFILIATION: Lundberg Laboratory for Cancer Research, Sahlgrenska University Hospital, SE-413 45 Göteborg, Sweden. viktor.johanson@medfak.gu.se

Country: England

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MEDLINETA: Endocr Relat Cancer

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