Inhibition of HIV-1 Tat activity correlates with down-regulation of bcl-2 and results in reduction of angiogenesis and oncogenicity.
The Tat protein of the human immunodeficiency virus type 1 promotes survival and growth and inhibits apoptosis of different cell types. These effects of Tat are attributed to the induction of bcl-2 gene expression. In this study we show that the blocking of both intracellular and extracellular Tat correlates with a decrease of bcl-2 transcripts, leading in vitro to a lower growth rate and attenuation of the transformed phenotype and in vivo to a reduced angiogenic and oncogenic activity of Tat-expressing cells. These results support the notion that bcl-2 is an effector of Tat-induced angiogenesis and oncogenesis and indicate that the blocking of Tat functions by immunoprophylactic, pharmacological, and gene therapy approaches may help to control oncogenesis during AIDS.
Corallini
Alfredo
A
Department of Experimental and Diagnostic Medicine, Section of Microbiology, Center of Biotechnology, University of Ferrara, I-44100 Ferrara, Italy.
Sampaolesi
Riccardo
R
Possati
Laura
L
Merlin
Michela
M
Bagnarelli
Patrizia
P
Piola
Catia
C
Fabris
Marina
M
Menegatti
Maria Agnese
MA
Talevi
Simona
S
Gibellini
Davide
D
Rocchetti
Romina
R
Caputo
Antonella
A
Barbanti-Brodano
Giuseppe
G
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016375:Antisense Elements (Genetics); D017209:Apoptosis; D015197:Carcinogenicity Tests; D004214:Distamycins / Q000494:pharmacology; D015536:Down-Regulation; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D015696:Gene Products, tat / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015497:HIV-1; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D014407:Tumor Cells, Cultured; D054322:tat Gene Products, Human Immunodeficiency Virus
D000906:Antibodies; D016375:Antisense Elements (Genetics); D004214:Distamycins; D015696:Gene Products, tat; C113015:PNU 153429; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D054322:tat Gene Products, Human Immunodeficiency Virus