PMID- 16862449 OWN - NLM STAT- MEDLINE DCOM- 20070403 LR - 20181113 IS - 0300-8177 (Print) IS - 0300-8177 (Linking) VI - 295 IP - 1-2 DP - 2007 Jan TI - The Trk tyrosine kinase inhibitor K252a regulates growth of lung adenocarcinomas. PG - 19-26 AB - 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. FAU - Perez-Pinera, P AU - Perez-Pinera P AD - Departamento de Morfologia y Biologia Celular, Facultad de Medicina, Universidad de Oviedo, Julian Claveria S/N, Oviedo, Spain. pab_correo@yahoo.com FAU - Hernandez, T AU - Hernandez T FAU - Garcia-Suarez, O AU - Garcia-Suarez O FAU - de Carlos, F AU - de Carlos F FAU - Germana, A AU - Germana A FAU - Del Valle, M AU - Del Valle M FAU - Astudillo, A AU - Astudillo A FAU - Vega, J A AU - Vega JA LA - eng PT - Journal Article DEP - 20060722 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Carbazoles) RN - 0 (Indole Alkaloids) RN - 0 (Nerve Growth Factors) RN - 0 (RNA, Messenger) RN - 17885-08-4 (Phosphoserine) RN - 97161-97-2 (staurosporine aglycone) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) RN - EC 2.7.10.1 (Receptor, trkA) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.10.1 (Receptor, trkC) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Adenocarcinoma/*enzymology/genetics/*pathology MH - Adult MH - Apoptosis/drug effects MH - Carbazoles/*pharmacology MH - Caspase 3/metabolism MH - Cell Line, Tumor MH - Dose-Response Relationship, Drug MH - Enzyme Activation/drug effects MH - Female MH - Gene Expression Regulation, Neoplastic/drug effects MH - Humans MH - Indole Alkaloids MH - Lung Neoplasms/*enzymology/genetics/*pathology MH - Male MH - Middle Aged MH - Nerve Growth Factors/genetics/metabolism MH - Phosphorylation/drug effects MH - Phosphoserine/metabolism MH - Proto-Oncogene Proteins c-akt/metabolism MH - RNA, Messenger/genetics/metabolism MH - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/genetics/metabolism MH - Receptor, trkA/antagonists & inhibitors/genetics/metabolism MH - Receptor, trkB/antagonists & inhibitors/genetics/metabolism MH - Receptor, trkC/antagonists & inhibitors/genetics/metabolism MH - Tumor Stem Cell Assay EDAT- 2006/07/25 09:00 MHDA- 2007/04/04 09:00 CRDT- 2006/07/25 09:00 PHST- 2006/03/08 00:00 [received] PHST- 2006/06/26 00:00 [accepted] PHST- 2006/07/25 09:00 [pubmed] PHST- 2007/04/04 09:00 [medline] PHST- 2006/07/25 09:00 [entrez] AID - 10.1007/s11010-006-9267-7 [doi] PST - ppublish SO - Mol Cell Biochem. 2007 Jan;295(1-2):19-26. doi: 10.1007/s11010-006-9267-7. Epub 2006 Jul 22.