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A transplantable hu...
A transplantable human medullary thyroid carcinoma as a model for RET tyrosine kinase-driven tumorigenesis
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- Johanson, Viktor, 1958 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Ahlman, Håkan, 1947 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Bernhardt, Peter, 1966 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Jansson, Svante, 1948 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Kölby, Lars, 1963 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Persson, Fredrik, 1973 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Stenman, Göran, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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- Swärd, Christina, 1967 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Wängberg, Bo, 1953 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper,Institute of Clinical Sciences
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- Stridsberg, Mats (författare)
- Uppsala universitet,Klinisk kemi,Clinical Chemistry
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- Nilsson, Ola, 1957 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för patologi,Institute of Biomedicine, Department of Pathology
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(creator_code:org_t)
- 2007
- 2007
- Engelska.
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Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 14:2, s. 433-444
- Relaterad länk:
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
Ämnesord
Stäng
- 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.
Nyckelord
- Aged
- Animals
- Calcitonin/blood
- Carcinoma; Medullary/*drug therapy/enzymology/pathology
- Cell Line
- Tumor
- Cell Transformation
- Neoplastic/drug effects
- Chromogranin A/blood
- Disease Models
- Animal
- Humans
- Karyotyping
- Male
- Mice
- Mice
- Nude
- Mutation
- Piperidines/pharmacology
- Protein Kinase Inhibitors/pharmacology
- Protein-Tyrosine Kinases/antagonists & inhibitors/genetics/metabolism
- Proto-Oncogene Proteins c-ret/*antagonists & inhibitors/genetics/metabolism
- Quinazolines/pharmacology
- Receptor
- Epidermal Growth Factor/antagonists & inhibitors
- Thyroid Neoplasms/*drug therapy/enzymology/pathology
- Vascular Endothelial Growth Factor Receptor-1/antagonists & inhibitors
- Xenograft Model Antitumor Assays
- MEDICINE
- MEDICIN
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
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Johanson, Viktor ...
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Ahlman, Håkan, 1 ...
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Bernhardt, Peter ...
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Jansson, Svante, ...
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Kölby, Lars, 196 ...
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Persson, Fredrik ...
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visa fler...
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Stenman, Göran, ...
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Swärd, Christina ...
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Wängberg, Bo, 19 ...
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Stridsberg, Mats
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Nilsson, Ola, 19 ...
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visa färre...
- Artiklar i publikationen
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Endocrine-Relate ...
- Av lärosätet
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Uppsala universitet
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Göteborgs universitet