PMID- 17628821
OWN - NLM
STAT- MEDLINE
DCOM- 20080410
LR  - 20181201
IS  - 0937-4477 (Print)
IS  - 0937-4477 (Linking)
VI  - 264
IP  - 12
DP  - 2007 Dec
TI  - Signal transduction-related gene transfer leads to inhibition of proliferation 
      and induction of differentiation in laryngeal squamous cell carcinoma in vitro.
PG  - 1467-73
AB  - The aim of this study is to target the interference therapy of signal 
      transduction which is a novel therapeutic strategy in laryngeal squamous cell 
      carcinoma (LSCC). We successfully constructed recombinant adenoviruses Ad-p14ARF, 
      and Ad-antisense EGFR using AdEasy-1 vector System. Clonogenic cell assay, 
      western blotting assay, 3'(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium 
      bromide (MTT) assay, flow cytometer (FCM) assay, and immunocytochemical technique 
      were designed to examine the inhibition of proliferation, protein expression of 
      p14ARF and EGFR and induction of differentiation, respectively. Furthermore the 
      synergistic effect of Ad-p14ARF and Ad-antisense EGFR on Hep-2 cell was examined. 
      We successfully used AdEasy-1 vector system to construct recombinant adenoviruses 
      Ad-p14ARF and Ad-antisense EGFR. The activity of proliferation of Hep-2 cells was 
      inhibited markedly by infecting Ad-p14ARF or Ad-antisense EGFR by comparing 
      Ad-sense EGFR (P=0.005) with vector control (Ad-Ctrl) (P=0.005) and with PBS 
      (P=0.003). This effect, combining Ad-antisense-EGFR with Ad-p14ARF became more 
      noticeable than alone (P=0.01, P=0.02, respectively). P14 ARF protein 
      overexpression, EGFR protein down expression, and inhibition of proliferation 
      were observed in Hep-2 cells infected by either Ad-p14ARF or Ad-antisense EGFR. 
      FCM revealed that the proportion of apoptosis cells transfected by Ad-p14ARF and 
      Ad-antisense EGFR increased more obviously than the control. The proportion of 
      (Hep-2 cells in) G0/G1 phases was increased by up to 78.5, 77.7, and 86.9% in 
      Ad-antisense EGFR, Ad-p14ARF, and Ad-antisense EGFR+Ad-p14ARF, respectively. Our 
      findings demonstrated that not only EGFR but p14ARF also plays a major role on 
      the genesis and in modulating the cell growth and differentiation of human 
      laryngocarcinoma. They efficaciously blocked the signal transduction of human 
      laryngocarcinoma cell, and may therefore, be an effective potential target of 
      gene therapy to prevent human laryngocarcinoma cell proliferation.
FAU - Xian, Junming
AU  - Xian J
AD  - Department of Otolaryngology, State Key Laboratory of Biotherapy, West China 
      Hospital, Sichuan University, 37# Guoxue Street, Chengdu, 610041, People's 
      Republic of China.
FAU - Lin, Yinghe
AU  - Lin Y
FAU - Liu, Yafeng
AU  - Liu Y
FAU - Gong, Ping
AU  - Gong P
FAU - Liu, Shixi
AU  - Liu S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070713
PL  - Germany
TA  - Eur Arch Otorhinolaryngol
JT  - European archives of oto-rhino-laryngology : official journal of the European 
      Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the 
      German Society for Oto-Rhino-Laryngology - Head and Neck Surgery
JID - 9002937
RN  - 0 (Tumor Suppressor Protein p14ARF)
RN  - EC 2.7.10.1 (ErbB Receptors)
SB  - IM
MH  - Adenoviridae
MH  - Carcinoma, Squamous Cell/*pathology/therapy
MH  - Cell Culture Techniques
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - ErbB Receptors/*genetics
MH  - *Gene Transfer Techniques
MH  - Genetic Vectors
MH  - Humans
MH  - Laryngeal Neoplasms/*pathology/therapy
MH  - Signal Transduction/*genetics
MH  - Tumor Suppressor Protein p14ARF/*genetics
EDAT- 2007/07/14 09:00
MHDA- 2008/04/11 09:00
CRDT- 2007/07/14 09:00
PHST- 2006/11/09 00:00 [received]
PHST- 2007/06/22 00:00 [accepted]
PHST- 2007/07/14 09:00 [pubmed]
PHST- 2008/04/11 09:00 [medline]
PHST- 2007/07/14 09:00 [entrez]
AID - 10.1007/s00405-007-0392-z [doi]
PST - ppublish
SO  - Eur Arch Otorhinolaryngol. 2007 Dec;264(12):1467-73. doi: 
      10.1007/s00405-007-0392-z. Epub 2007 Jul 13.