Up-regulation of focal adhesion kinase in non-small cell lung cancer

被引:98
作者
Carelli, Stephana
Zadra, Giorgia
Vaira, Valentina
Falleni, Monica
Bottiglieri, Luca
Nosotti, Mario
Di Giulio, Anna Maria
Gorio, Alfredo
Bosari, Silvano
机构
[1] Univ Milan, Dept Med Surg & Dent, Pharmacol Lab, I-20142 Milan, Italy
[2] IRCCS Humanitas, Clin Pharmacol, Milan, Italy
[3] Univ Milan, AO San Paolo, Dept Med Surg & Dent, Div Pathol, Milan, Italy
[4] Regina Elena & Mangiagalli, Fdn Osped Maggiore Policlin, Div Thorac Surg, Milan, Italy
关键词
FAK; NSCLC; tumourigenesis; cell migration; cancer progression; immunohistochemistry; real-time RT-PCR;
D O I
10.1016/j.lungcan.2006.06.001
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase linked to the integrin and growth factor receptor-signalling pathways that regulates a number of the biological processes involved in neoplastic transformation, invasion and metastases, such as cell adhesion, migration and apoptosis. Its up-regulation might play a role in the tumourigenesis of invasive tumours, but its involvement in human lung cancer tissues has not yet been determined. We immunohistochemically compared FAK expression and localisation in 60 formalin-fixed and paraffin-embedded non-small cell lung cancer (NSCLC) tissues with that in the surrounding non-neoplastic tissue and in a further five microscopically normal lungs. FAK mRNA levels were quantitatively determined by real-time RT-PCR in frozen tissue specimens of all of the tumours and 21 matched non-neoplastic lung parenchymas, and protein expression in 16 homogenates of the matched neoplastic/non-neoplastic specimens was evaluated by Western blotting. The three different techniques showed that FAK is weakly expressed in non-neoplastic lung parenchyma and up-regulated in NSCLCs. Moreover, Western blotting and real-time RT-PCR indicated a statistically significant correlation between FAK up-regulation and higher disease stages (I + II versus III + IV, p=0.019 and 0.028, respectively). Our results provide evidence that FAK is up-regulated in NSCLCs, and suggest its potential involvement in lung cancer progression. (C) 2006 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:263 / 271
页数:9
相关论文
共 46 条
[1]   Cell adhesion molecules, signal transduction and cell growth [J].
Aplin, AE ;
Howe, AK ;
Juliano, RL .
CURRENT OPINION IN CELL BIOLOGY, 1999, 11 (06) :737-744
[2]   Ionizing radiation modules of the expression and tyrosine phosphorylation of the focal adhesion-associated proteins focal adhesion kinase (FAK) and its substrates p130cas and paxillin in A549 human lung carcinoma cells in vitro [J].
Beinke, C ;
Van Beuningen, D ;
Cordes, N .
INTERNATIONAL JOURNAL OF RADIATION BIOLOGY, 2003, 79 (09) :721-731
[3]  
Cance WG, 2000, CLIN CANCER RES, V6, P2417
[4]  
Cary LA, 1996, J CELL SCI, V109, P1787
[5]   ASSOCIATION OF FOCAL ADHESION KINASE WITH ITS POTENTIAL SUBSTRATE PHOSPHATIDYLINOSITOL 3-KINASE [J].
CHEN, HC ;
GUAN, JL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (21) :10148-10152
[6]   STABLE ASSOCIATION OF PP60(SRC) AND PP59(FYN) WITH THE FOCAL ADHESION-ASSOCIATED PROTEIN-TYROSINE KINASE, PP125(FAK) [J].
COBB, BS ;
SCHALLER, MD ;
LEU, TH ;
PARSONS, JT .
MOLECULAR AND CELLULAR BIOLOGY, 1994, 14 (01) :147-155
[7]   Focal adhesion kinase gene silencing promotes anoikis and suppresses metastasis of human pancreatic adenocarcinoma cells [J].
Duxbury, MS ;
Ito, H ;
Zinner, MJ ;
Ashley, SW ;
Whang, EE .
SURGERY, 2004, 135 (05) :555-562
[8]   RNA interference targeting focal adhesion kinase enhances pancreatic adenocarcinoma gemcitabine chemosensitivity [J].
Duxbury, MS ;
Ito, H ;
Benoit, E ;
Zinner, MJ ;
Ashley, SW ;
Whang, EE .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2003, 311 (03) :786-792
[9]   Survivin gene expression in early-stage non-small cell lung cancer [J].
Falleni, M ;
Pellegrini, C ;
Marchetti, A ;
Oprandi, B ;
Buttitta, F ;
Barassi, F ;
Santambrogio, L ;
Coggi, G ;
Bosari, S .
JOURNAL OF PATHOLOGY, 2003, 200 (05) :620-626
[10]   Focal adhesion kinase is overexpressed in hepatocellular carcinoma and can be served as an independent prognostic factor [J].
Fujii, T ;
Koshikawa, K ;
Nomoto, S ;
Okochi, O ;
Kaneko, T ;
Inoue, S ;
Yatabe, Y ;
Takeda, S ;
Nakao, A .
JOURNAL OF HEPATOLOGY, 2004, 41 (01) :104-111