title: RASEF is a novel diagnostic biomarker and a therapeutic target for lung cancer.
abstract: Genome-wide gene expression profiling revealed that the Ras and EF-hand domain containing (RASEF) transcript was significantly transactivated in the majority of lung cancers. Using lung cancer cells, transient expression of RASEF promoted cell growth, whereas RASEF knockdown not only reduced its expression but resulted in growth suppression of the cancer cells. Immunohistochemical staining using tumor tissue microarrays consisting of 341 archived non-small cell lung cancers (NSCLC) revealed the association of strong RASEF positivity with poor prognosis (P = 0.0034 by multivariate analysis). Mechanistically, RASEF interacted with extracellular signal-regulated kinase (ERK) 1/2 and enhanced ERK1/2 signaling. Importantly, inhibiting the interaction between RASEF and ERK1/2 using a cell-permeable peptide that corresponded to the ERK1/2-interacting site of RASEF, suppressed growth of lung cancer cells. This study demonstrates that elevated RASEF promoted cell growth via enhanced ERK signaling and is associated with poor prognosis of NSCLC.
  
  
  CONCLUSIONS
  RASEF may play an important role in lung carcinogenesis and could serve as a vaiable prognostic biomarker and target for the development of new molecular therapies.
authors.affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, USA.
authors.forename: Hideto
authors.initials: H
authors.lastname: Oshita
authors.forename: Ryohei
authors.initials: R
authors.lastname: Nishino
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takano
authors.forename: Takashi
authors.initials: T
authors.lastname: Fujitomo
authors.forename: Masato
authors.initials: M
authors.lastname: Aragaki
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kato
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Akiyama
authors.forename: Eiju
authors.initials: E
authors.lastname: Tsuchiya
authors.forename: Nobuoki
authors.initials: N
authors.lastname: Kohno
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Yataro
authors.initials: Y
authors.lastname: Daigo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D011379:Prognosis; D020663:ras Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; C529641:RASEF protein, human; D020663:ras Guanine Nucleotide Exchange Factors