HIV type 1 Tat protein is a survival factor for Kaposi's sarcoma and endothelial cells.
The HIV-1 Tat protein has been directly implicated in the pathogenesis of AIDS-related Kaposi's sarcoma (KS); however, its effects on KS spindle-shaped and endothelial cell apoptosis are largely unexplored. Since susceptibility to apoptosis is relevant for tumor development and response to therapy, we investigated the effects of Tat on KS and endothelial cell survival from apoptosis. The effect of Tat was evaluated in three KS cell lines (KS-imm, KS-C1, and KS-L3) exposed to the chemotherapy agent vincristine, currently used for the treatment of this tumor, and in human umbilical vein-derived endothelial cells (HUVECs) induced to undergo apoptosis by serum withdrawal. Apoptosis was assessed by enzymatic assays, microscopic examination of chromatin and cytoskeleton, evaluation of plasma membrane integrity and subdiploid DNA content, TUNEL assays, and measurement of caspase-3 activity. Tat, in a dose-dependent manner, protected the three KS cell lines and HUVECs from apoptosis induced by vincristine or serum starvation, respectively. This effect appeared to be independent of modulation of Fas, Bcl-2, or Bax expression. In contrast, Tat upregulated Bcl-X(L) expression and induced a relevant decrease in caspase-3 activity in vincristine-treated KS cells. Taken together, these results suggest that the HIV-1 Tat protein may factor KS development and progression by sustaining endothelial and transformed cell survival.
Cantaluppi
V
V
Cattedra di Nefrologia, Dipartimento di Medicina Interna, Università di Torino, Turin, Italy.
Biancone
L
L
Boccellino
M
M
Doublier
S
S
Benelli
R
R
Carlone
S
S
Albini
A
A
Camussi
G
G
D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival; D004730:Endothelium, Vascular / Q000187:drug effects; D005434:Flow Cytometry; D015696:Gene Products, tat / Q000502:physiology*; D015497:HIV-1; D006801:Humans; D007124:Immunoenzyme Techniques; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects*; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D014407:Tumor Cells, Cultured; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation; D014750:Vincristine / Q000627:therapeutic use; D051020:bcl-X Protein; D054322:tat Gene Products, Human Immunodeficiency Virus
C494811:BCL2L1 protein, human; D015696:Gene Products, tat; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; D054322:tat Gene Products, Human Immunodeficiency Virus; D014750:Vincristine; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases