Τίτλος:
RETRACTED: 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(uPAR) and sense p16 genes (Retracted article. See vol. 295, pg. 13134,
2020)
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 phe. notype. 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
El-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.
Συγγραφείς:
Adachi, Y
Lakka, SS
Chandrasekar, N
Yanamandra, N
Gondi,
CS
Mohanam, S
Dinh, DH
Olivero, WC
Gujrati, M and
Tamiya, T
Ohmoto, T
Kouraklis, G
Aggarwal, B
Rao, JS
Περιοδικό:
Journal of Biological Chemistry
Εκδότης:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI:
10.1074/jbc.M104334200
