Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes
Authors: C S Gondi
W C Olivero
G Kouraklis
S Mohanam
B Aggarwal
N Yanamandra
J S Rao
N Chandrasekar
T Tamiya
S S Lakka
D H Dinh
Y Adachi
M Gujrati
T Ohmoto
Journal: Journal of Biological Chemistry (2001)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: extracellular matrix; integrin receptors; cell adhesion; intracellular signaling; cell migration
Affiliations: Department of Biomedical Therapeutic Sciences, Division of Cancer Biology, University of Illinois College of Medicine, Peoria, IL 61656, USA.

Abstract:  Interaction between the extracellular matrix and integrin receptors on cell surfaces leads not only to cell adhesion but also to intracellular signaling events that affect cell migration, proliferation, and survival. The vitronectin receptor alpha(v)beta(3) integrin is of key importance in glioma cell biology. The expression of urokinase-type plasminogen activator receptor (uPAR) was recently shown to co-regulate with the expression of alpha(v)beta(3) integrin. Moreover, restoration of the p16 protein in glioma cells inhibits the alpha(v)beta(3) integrin-mediated spreading of those cells on vitronectin. Thus we hypothesized that adenovirus-mediated down-regulation of uPAR and overexpression of p16 might down-regulate the expression of alpha(v)beta(3) integrin and the integrin-mediated signaling in glioma cells, thereby defeating the malignant phenotype. In this study, we used replication-deficient adenovirus vectors that contain either a uPAR antisense expression cassette (Ad-uPAR) or wild-type p16 cDNA (Ad-p16) and a bicistronic adenovirus construct in which both the uPAR antisense and p16 sense expression cassettes (Ad-uPAR/p16) are inserted in the E1-deleted region of the vector. Infecting the malignant glioma cell line SNB19 with Ad-uPAR, Ad-p16, or Ad-uPAR/p16 in the presence of vitronectin resulted in decreased alpha(v)beta(3) integrin expression and integrin-mediated biological effects, including adhesion, migration, proliferation, and survival Our results support the therapeutic potential of simultaneously targeting uPAR and p16 in the treatment of gliomas. 

Retracted: Yes

PubPeer comments:
 Figure 1 and Figure 8 appear to show the same alpha-Tubulin panel, but the loading order of samples is slightly different. ![file] , 
 Down-regulation of integrin alpha(v)beta(3) expression and integrin-mediated signaling in glioma cells by adenovirus-mediated transfer of antisense urokinase-type plasminogen activator receptor (uPAR) and sense p16 genes pubmed: 11572856 doi: 10.1074 jbc.m104334200 issn: 0021-9258 issn: 1083-351x Yoshiaki Adachi , Sajani S. Lakka , Nirmala Chandrasekar , Niranjan Yanamandra , Christopher S. Gondi , Sanjeeva Mohanam , Dzeng H. Dinh , William C. Olivero , Meena Gujrati , Takashi Tamiya , Takashi Ohmoto , Gregory Kouraklis , Bharat Aggarwal , Jasti S. Rao The Journal of biological chemistry (2001) VOLUME 276 (2001) PAGES 47171u201347177 This article has been retracted by the publisher. Yoshiaki Adachi, Nirmala Chandrasekar, Dzeng H. Dinh, Takashi Tamiya, Takashi Ohmoto, and Jasti S. Rao could not be reached for comment. The tubulin immunoblot in Fig. 1 was reused in Fig. 8. Upon further investigation, there was also an additional discrepancy in the total Akt immunoblot between the Paper in Press version of Fig. 8 and the final version of Fig 8. u2022tu00a9 2020 by The American Society for Biochemistry and Molecular Biology, Inc. ,