Molecular and Cellular Biochemistry

, Volume 295, Issue 1, pp 19–26

The Trk tyrosine kinase inhibitor K252a regulates growth of lung adenocarcinomas

Authors

    • Departamento de Morfología y Biología Celular, Facultad de MedicinaUniversidad de Oviedo
  • T. Hernandez
    • Medicina, Especialidades Médico-QuirúrgicasUniversidad de Oviedo
  • O. García-Suárez
    • Departamento de Morfología y Biología Celular, Facultad de MedicinaUniversidad de Oviedo
  • F. de Carlos
    • Medicina, Especialidades Médico-QuirúrgicasUniversidad de Oviedo
  • A. Germana
    • Dipartimento di Morfologia, Biochimica, Fisiologia e Produzione Animale, Sezione di MorfologiaUniversita di Messina
  • M. del Valle
    • Departamento de Morfología y Biología Celular, Facultad de MedicinaUniversidad de Oviedo
  • A. Astudillo
    • Medicina, Especialidades Médico-QuirúrgicasUniversidad de Oviedo
    • Instituto Universitario de OncologíaUniversidad de Oviedo
  • J. A. Vega
    • Instituto Universitario de OncologíaUniversidad de Oviedo
    • Anatomía y Embriología, Facultad de MedicinaUniversidad San Pablo-CEU
Article

DOI: 10.1007/s11010-006-9267-7

Cite this article as:
Perez-Pinera, P., Hernandez, T., García-Suárez, O. et al. Mol Cell Biochem (2007) 295: 19. doi:10.1007/s11010-006-9267-7

Abstract

The neurotrophin family of growth factors and their receptors support the survival of several neuronal and non-neuronal cell populations during embryonic development and adult life. Neurotrophins are also involved in malignant transformation. To seek the role of neurotrophin signaling in human lung cancer we studied the expression of neurotrophin receptors in human lung adenocarcinomas and investigated the effect of the neurotrophin receptor inhibitor K252a in A549 cell survival and colony formation ability in soft agar. We showed that human lung adenocarcinomas express TrkA and TrkB, but not TrkC; A549 cells, derived from a human lung adenocarcinoma, express mRNA transcripts encoding nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), TrkA, TrkB, and p75, and high protein levels of TrkA and TrkB. Stimulation of cells using NGF or BDNF activates the anti-apoptotic protein Akt. Interestingly, inhibition of neurotrophin receptor signaling using K252a prevents Akt activation in response to NGF or BDNF, induces apoptotic cell death, and diminishes the ability of A549 cells to growth in soft agar. The data suggest that neurotrophin signaling inhibition using k252a may be a valid therapy to treat patients with lung adenocarcinomas.

Keywords

neurotrophinTrkstumorlungadenocarcinomak252a

Copyright information

© Springer Science+Business Media, Inc. 2006