Immunohistochemical Detection of Bcl-2 in Kaposi's Sarcoma Lesions Varies According to Histopathologic Stage, Whereas Expression of Bcl-x and Mcl-1 Differs According to Human Immunodeficiency Virus Serologic Status of Patients

Fernández‐Figueras, María‐Teresa; Puig, L.; Fernández-Vasalo, Angela; Esquius, Mireia; Montero, María-Angeles; Ariza, Aurelio

doi:10.1038/modpathol.3880075

Cited by 11 publications

(9 citation statements)

References 31 publications

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“…Mcl-1 is an anti-apoptotic protein that has been shown to decrease in response to flavopiridol treatment in leukemia cells and other types of cancer cells (43). In addition, it was reported that Mcl-1 increases in AIDS-related malignancies (44,45). Consistent with these observations, our results demonstrate that the overall level of Mcl-1 is higher in infected cells (ACH2) than in uninfected cells (CEM) (Fig.…”

Section: Hiv-1 Infection Ensures a Balance Between Cell Survival And supporting

confidence: 81%

Identifying the Membrane Proteome of HIV-1 Latently Infected Cells

Berro

Fuente

Klase

et al. 2007

Journal of Biological Chemistry

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Profiling integral plasma membrane proteins is of particular importance for the identification of new biomarkers for diagnosis and for drug development. We report in this study the identification of surface markers by performing comparative proteomics of established human immunodeficiency virus-1 (HIV-1) latent cell models and parental cell lines. To this end we isolated integral membrane proteins using a biotin-directed affinity purification method. Isolated proteins were separated by two-dimensional gel electrophoresis and identified by matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) after in gel digestion. Seventeen different proteins were found to vary on the surface of T-cells due to HIV-1 infection. Of these proteins, 47% were integral membrane proteins, and 18% were membrane-associated. Through the use of complementary techniques such as Western blotting and fluorescent staining, we confirmed the differential expression of some of the proteins identified by MALDI-TOF including Bruton's tyrosine kinase and X-linked inhibitor of apoptosis. Finally, using phosphatidylinositol 3-kinase inhibitors and flavopiridol to inhibit Bruton's tyrosine kinase localization at the membrane and X-linked inhibitor of apoptosis protein expression, respectively, we showed that HIV-1 latently infected cells are more sensitive to these drugs than uninfected cells. This suggests that HIV-1 latently infected cells may be targeted with drugs that alter several pathways that are essential for the establishment and maintenance of latency.Biological membranes surround and compartmentalize cells. They provide a physical boundary between the cell and its environment and play an important role in cellular homoeostasis and metabolic energy transduction. According to the SingerNicolson "fluid-mosaic model" (1), plasma membranes are organized into lipid bilayers containing proteins that can diffuse rapidly throughout the two-dimensional surface of the membrane. Membrane proteins typically make up around a third of the proteome of a cell and associate with the membrane in different ways. Integral membrane proteins are contained within the bilayer through one or more transmembrane regions. They can also be associated with lipid anchors such as fatty acids and can cover large regions of a membrane with protein surfaces. Alternatively, proteins can be associated with the membrane through non-covalent interactions with integral membrane proteins or other membrane-associated proteins. The fluidity differences and the organization of protein and lipids within the plasma membrane depend upon the cholesterol content in the bilayer (2). The current evidence supports a novel concept of specific microdomains existing in the plasma membrane in vivo in regions rich in cholesterol (2, 3). These specific microdomains, termed "lipid rafts," are composed of tightly packed sphingolipids, gangliosides, and cholesterol (4). Lipid rafts are generally small, ranging from 25 to 700 nm depending on the activation state of the cell (5). In ad...

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Section: Hiv-1 Infection Ensures a Balance Between Cell Survival And supporting

confidence: 81%

Identifying the Membrane Proteome of HIV-1 Latently Infected Cells

Berro

Fuente

Klase

et al. 2007

Journal of Biological Chemistry

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“…In fact, Bcl-2 protein levels augment in late-stage, as compared to early-stage, KS lesions, and this parallels a decrease in vascular cell apoptosis [8–12]. …”

Section: Discussionmentioning

confidence: 99%

“…In this context, the protein levels of Bcl-2, a potent antagonist of programmed cell death (apoptosis), were found to be increased in late-stage, as compared to early-stage, lesions from all forms of KS [8–12]. Coexpression of Bcl-2 and endothelial cell markers [9, 10] indicates that Bcl-2 is upregulated in activated endothelial cells lining the newly formed, abnormal blood vessels characterizing KS lesions.…”

Section: Introductionmentioning

confidence: 99%

Fibroblast Growth Factor-2 and the HIV-1 Tat Protein Synergize in Promoting Bcl-2 Expression and Preventing Endothelial Cell Apoptosis: Implications for the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

Sgadari

Barillari

Palladino

et al. 2011

International Journal of Vascular Medicine

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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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“…Skin samples of psoriasis that are known to exhibit high expression of HBD-3 and LL-37 in the epidermis were used as positive controls. Immunostaining results of dermal lesions of KS were scored as previously described 29 . Immunoreactivity of HBD-3 and LL-37 were evaluated in the two basic component of this disease (spindle-shaped cells and endothelial cells of newly formed vessels).…”

Section: Methodsmentioning

confidence: 99%

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

2012

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Background: Kaposi’s sarcoma (KS) is a rare neoplasm of lymphatic endothelial cells. Human herpes virus 8 (HHV-8) is considered to be a necessary, but not sufficient causal agent of KS and additional cofactors remain unknown. In this study we evaluated the expression of human β defensin (HBD)-3 and LL-37 in cutaneous lesions of KS in comparison to the healthy skin of normal subjects. Methods: We performed a quantitative immunohistochemical study of HBD-3 and LL-37 on skin lesions from 18 patients having KS, and on healthy skin from 12 normal controls. Results: HBD-3 and LL-37 were significantly upregulated in epidermal and dermal specimens of all KS patients in comparison to normal skin of healthy controls. The immunostaining score of dermal HBD-3 was significantly higher in nodular lesions (9.6 ± 2.4) versus plaque lesions (4.1 ± 2.2), P = 0.001. Also the immunostaining score of dermal LL-37 was significantly higher in nodular lesions versus plaque lesions (P = 0.001). Conclusions: We have demonstrated for the first time that HBD-3 and LL-37 are significantly upregulated in lesional skin of KS in comparison to the skin of healthy controls. The obtained data suggest a possible involvement of these antimicrobial peptides in the pathogenesis of KS. However, the biological significance of HBD-3 and LL-37 in KS lesions needs further research.

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Immunohistochemical Detection of Bcl-2 in Kaposi's Sarcoma Lesions Varies According to Histopathologic Stage, Whereas Expression of Bcl-x and Mcl-1 Differs According to Human Immunodeficiency Virus Serologic Status of Patients

Cited by 11 publications

References 31 publications

Identifying the Membrane Proteome of HIV-1 Latently Infected Cells

Identifying the Membrane Proteome of HIV-1 Latently Infected Cells

Fibroblast Growth Factor-2 and the HIV-1 Tat Protein Synergize in Promoting Bcl-2 Expression and Preventing Endothelial Cell Apoptosis: Implications for the Pathogenesis of AIDS-Associated Kaposi's Sarcoma

Upregulation of human β-defensin-3 and cathelicidin LL-37 in Kaposi’s sarcoma

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