Abstract
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-XL 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.
| Original language | English |
|---|---|
| Pages (from-to) | 965-976 |
| Number of pages | 12 |
| Journal | AIDS Research and Human Retroviruses |
| Volume | 17 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2001 |
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ASJC Scopus subject areas
- Immunology
- Virology
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HIV type 1 Tat protein is a survival factor for kaposi's sarcoma and endothelial cells. / Cantaluppi, V.; Biancone, L.; Boccellino, M.; Doublier, S.; Benelli, R.; Carlone, S.; Albini, A.; Camussi, G.
In: AIDS Research and Human Retroviruses, Vol. 17, No. 10, 2001, p. 965-976.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - HIV type 1 Tat protein is a survival factor for kaposi's sarcoma and endothelial cells
AU - Cantaluppi, V.
AU - Biancone, L.
AU - Boccellino, M.
AU - Doublier, S.
AU - Benelli, R.
AU - Carlone, S.
AU - Albini, A.
AU - Camussi, G.
PY - 2001
Y1 - 2001
N2 - 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-XL 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.
AB - 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-XL 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.
UR - http://www.scopus.com/inward/record.url?scp=0034819783&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034819783&partnerID=8YFLogxK
U2 - 10.1089/088922201750290087
DO - 10.1089/088922201750290087
M3 - Article
C2 - 11461682
AN - SCOPUS:0034819783
VL - 17
SP - 965
EP - 976
JO - AIDS Research and Human Retroviruses
JF - AIDS Research and Human Retroviruses
SN - 0889-2229
IS - 10
ER -