Proteomic analysis reveals heat shock protein 70 has a key role in polycythemia Vera

Autor: Marisol Fernández, Ana Jiménez, Miguel Gallardo, Joaquin Martinez-Lopez, Santiago Barrio, Alberto Paradela, Rosa Maria Garcia-Martin, Enriqueta Albizua, Rosa Ayala, Santiago Redondo, Juan Pablo Albar, Alicia Arenas, Florinda Gilsanz, Oscar Toldos
Rok vydání: 2013
Předmět:
Zdroj: Molecular Cancer
Digital.CSIC. Repositorio Institucional del CSIC
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ISSN: 1476-4598
DOI: 10.1186/1476-4598-12-142
Popis: JAK-STAT signaling through the JAK2V617F mutation is central to the pathogenesis of myeloproliferative neoplasms (MPN). However, other events could precede the JAK2 mutation. The aim of this study is to analyze the phenotypic divergence between polycytemia vera (PV) and essential thrombocytemia (ET) to find novel therapeutics targets by a proteomic and functional approach to identify alternative routes to JAK2 activation. Through 2D-DIGE and mass spectrometry of granulocyte protein from 20 MPN samples, showed differential expression of HSP70 in PV and ET besides other 60 proteins. Immunohistochemistry of 46 MPN bone marrow samples confirmed HSP70 expression. The median of positive granulocytes was 80% in PV (SD 35%) vs. 23% in ET (SD 34.25%). In an ex vivo model KNK437 was used as an inhibition model assay of HSP70, showed dose-dependent inhibition of cell growth and burst formation unit erythroid (BFU-E) in PV and ET, increased apoptosis in the erythroid lineage, and decreased pJAK2 signaling, as well as a specific siRNA for HSP70. These data suggest a key role for HSP70 in proliferation and survival of the erythroid lineage in PV, and may represent a potential therapeutic target in MPN, especially in PV.
This research was supported by grants from the Spanish Health office FIS PI08402, FIS PI030345, PI071009 and PI12/01728 grants; RD12/10, Red de Cancer (Cancer Network of Excellence) from the Instituto de Salud Carlos III, Spain, Fundacion Mutua madrilène; Universidad Complutense groups CCG07-UCM/BIO-2555 (Santiago Barrio and Florinda Gilsanz), FMM and CRIS foundation for cancer research (Joaquin Martinez-Lopez). The Proteomics Facility of the Centro Nacional de Biotecnología is a member of ProteoRed-Spanish National Institute for Proteomics and follows the quality criteria set up by ProteoRed standards.
Databáze: OpenAIRE
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