TY - JOUR
T1 - Fibroblast growth factor-2 and the HIV-1 Tat protein synergize in promoting BCL-2 expression and preventing endothelial cell apoptosis
T2 - Implications for the pathogenesis of AIDS-associated kaposi's sarcoma
AU - Sgadari, Cecilia
AU - Barillari, Giovanni
AU - Palladino, Clelia
AU - Bellino, Stefania
AU - Taddeo, Brunella
AU - Toschi, Elena
AU - Ensoli, Barbara
PY - 2011
Y1 - 2011
N2 - Kaposi's sarcoma (KS) is a vascular tumor frequently occurring in Human Immunodeficiency Virus- (HIV-) 1-infected individuals. Our previous work indicated that the angiogenic fibroblast growth factor (FGF)-2 and the Tat protein of HIV-1, both expressed in KS lesions of HIV-infected patients, synergize at inducing angioproliferative, KS-like lesions in mice. Here we show that the development of angioproliferative lesions promoted in mice by combined Tat and FGF-2 associates with an increase in the levels of expression of the antiapoptotic Bcl-2 protein. Upregulation of Bcl-2 expression by combined FGF-2 and Tat occurs also in vitro, and this protects human primary endothelial cells from programmed cell death. As Bcl-2 is expressed in human KS lesions in a fashion paralleling the progression of the disease, these findings suggest a molecular mechanism by which Tat and FGF-2 cooperate in KS maintenance and progression in HIV-infected individuals.
AB - Kaposi's sarcoma (KS) is a vascular tumor frequently occurring in Human Immunodeficiency Virus- (HIV-) 1-infected individuals. Our previous work indicated that the angiogenic fibroblast growth factor (FGF)-2 and the Tat protein of HIV-1, both expressed in KS lesions of HIV-infected patients, synergize at inducing angioproliferative, KS-like lesions in mice. Here we show that the development of angioproliferative lesions promoted in mice by combined Tat and FGF-2 associates with an increase in the levels of expression of the antiapoptotic Bcl-2 protein. Upregulation of Bcl-2 expression by combined FGF-2 and Tat occurs also in vitro, and this protects human primary endothelial cells from programmed cell death. As Bcl-2 is expressed in human KS lesions in a fashion paralleling the progression of the disease, these findings suggest a molecular mechanism by which Tat and FGF-2 cooperate in KS maintenance and progression in HIV-infected individuals.
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U2 - 10.1155/2011/452729
DO - 10.1155/2011/452729
M3 - Article
AN - SCOPUS:84876409770
SN - 2090-2824
VL - 2011
JO - International Journal of Vascular Medicine
JF - International Journal of Vascular Medicine
M1 - 452729
ER -