The polycythemia vera-associated Jak2 V617F mutant induces tumorigenesis in nude mice
| Autor: | Megumi Funakoshi-Tago, Eriko Aizu-Yokota, Yoshiko Sonoda, Tadashi Kasahara, Kenji Tago, Jun Kamishimoto, Miyuki Abe |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Programmed cell death
Somatic cell Immunology Mutant Mice Nude Apoptosis Biology Transfection medicine.disease_cause Cell Line Mice hemic and lymphatic diseases medicine Animals Immunology and Allergy Genetic Predisposition to Disease Neoplasm Invasiveness Polycythemia Vera Pharmacology Polymorphism Genetic Cell growth food and beverages Janus Kinase 2 Tyrphostins Hematopoietic Stem Cells Cell Transformation Neoplastic Liver Cell culture Mutation Cancer research Carcinogenesis Neoplasm Transplantation Spleen hormones hormone substitutes and hormone antagonists |
| Zdroj: | International Immunopharmacology. 9:870-877 |
| ISSN: | 1567-5769 |
| DOI: | 10.1016/j.intimp.2009.03.011 |
| Popis: | The somatic Jak2 mutation (V617F) was identified in most patients with polycythemia vera (PV). Here, we show that the activating Jak2 V617F mutant completely protected Ba/F3 cells from cytokine withdrawal-induced apoptotic cell death. Interestingly, Ba/F3 cells expressing Jak2 V617F mutant induced rapid tumorigenesis in nude mice, leading to rapid death. Whereas an injection of Ba/F3 cells expressing wild-type Jak2 had no effect, an injection of Ba/F3 cells expressing Jak2 V617F mutant promptly invaded and spread into various distinct organs, such as the liver and spleen. Strikingly, Jak2 inhibitor, AG490 potently inhibited cytokine-independent cell growth induced by the Jak2 V617F mutant. Also, treatment with AG490 effectively delayed Jak2 V617F mutant-induced tumorigenesis in nude mice. Thus, our results both in vitro and in vivo suggest that Jak2 harboring V617F mutation is a potent oncogene able to promote cell transformation and tumorigenesis. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect