Conditional bioluminescent tmp3-alk cell line

Overexpression and activation of TMP3-ALK tyrosine kinase fusion protein is a causal oncogenic event in the development of Anaplastic Large Cell Lymphoma and Inflammatory Myofibroblastic ALK-positive tumors. Thus, the development of ALK specific tyrosine kinase inhibitors is a current therapeutic challenge. Animal models are essential to assess, in vivo, the efficiency of ALK-oncogene inhibitors and to identify new and/or additional therapeutic targets in the ALK tumorigenesis pathway. Using the tertracyclin system to allow conditional and concomitant TMP3-ALK and luciferase expression, we have developed a unique transplant model for bioluminescent TMP3-ALK-induced fibroblastic tumors in athymic nude mice. The reversible TPM3-ALK expression allowed us to demonstrate that this oncogene is essential for the tumor growth and its maintenance. In addition, we showed that this model could be used to precisely assess tumor growth inhibition upon ALK chemical inactivation. As proof of principle, we used the general tyrosine kinase inhibitor herbimycin A to inhibit ALK oncoprotein activity. This transplant model for TPM3-ALK-induced tumors represents a valuable tool not only to accurately and rapidly evaluate in vivo ALK-targeted therapies but also to gain insight into the mechanism of ALK-positive tumor development.

Interest / Relevance: Our model offer a new tool to investigate, in vitro and in vivo, the molecular mechanisms associated with ALK-induced lymphoproliferative disorders.
- To assess the mechanism of tyrosine kinase fusion oncoprotein positive tumor development
- To validate in vivo and in vitro the efficiency of specific ALK inhibitors
- To assess tumor growth inhibition upon chemical ALK inactivation
tyrosine kinase fusion oncoprotein induced tumors
Keywords: ALK tyrosine kinase oncogenesis , bioluminescence imaging , tetracycline system , tumour regression , targeted therapy
Scientist's name: Fabienne MEGGETTO-PRADELLE
Giuriato Sylvie

Reference:

RT00433

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Fabienne MEGGETTO-PRADELLE
Inserm Transfert
Research Tools
Organism: Mouse
Tissue: Fibroblastic cell line
Morphology: Myofibrosarcoma
Passage Number: Unknown
Subculture Routine: NA
Culture Medium: DMEM with 10% fetal calf serum, 20 ng/ml doxycycline and 1mg/ml G418
Growth Properties: Adherent
Karyotype: NA
Last update: 05/12/2019

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