Sustained nuclear localization of p21/WAF-1 upon growth arrest induced by contact inhibition

Ritt, Michelle G.; Mayor, Jocelyne; Wojcieszyn, John; Smith, Roger; Barton, Claudia L.; Modiano, Jaime F.

doi:10.1016/s0304-3835(00)00507-3

Cited by 40 publications

(49 citation statements)

References 29 publications

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“…Infection of the cell lines was verified microscopically by assessment of GFP fluorescence. As shown previously, 25,26 melanoma cells transfected with empty vectors showed negligible apoptosis. Each of the transduced (Fig 2a) or transfected (not shown) cell lines expressed detectable levels of FasL as Cr in the presence or absence of IL-2 for 16 hours.…”

Section: Induction Of Apoptosis Of Canine Melanoma Cells By Faslsupporting

confidence: 86%

“…Human FasL was transfected into the cells using cationic liposomes (Dosper, Roche Diagnostics, Chicago, IL). 26 A measure of 3 mg of the green-fluorescent protein (GFP) expression vector encoding hFasL was mixed with 9 mg of Dosper in 100 ml of HEPES-buffered saline and incubated for 15 minutes at 251C. The empty GFP vector was used as a negative control.…”

Section: Fasl Gene Deliverymentioning

confidence: 99%

“…To ensure that apoptosis was not mediated by the adenovirus vector, cell lines were also transfected with a plasmid encoding human FasL using cationic liposomes, 26 as well as with a control adenovirus vector expressing only the GFP tag. Infection of the cell lines was verified microscopically by assessment of GFP fluorescence.…”

Section: Induction Of Apoptosis Of Canine Melanoma Cells By Faslmentioning

confidence: 99%

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Enhancing antimelanoma immune responses through apoptosis

et al. 2003

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We examined the feasibility of using tumor apoptosis at accessible sites to enhance antimelanoma immune responses in a model of spontaneous canine melanoma. We show that priming peripheral blood mononuclear cells with apoptotic melanoma cells significantly enhanced autologous and allogeneic lymphokine-activated killing of tumor cells. Since various pathways required for intrinsic apoptosis are often inactivated in melanoma, we used Fas ligand (FasL) overexpression to promote extrinsic apoptosis. FasL induced apoptosis in five of six cell lines. Each of the susceptible lines, but not the resistant one, expressed Fas mRNA. In addition, direct intratumoral administration of FasL DNA to tumor-bearing dogs was safe, with no adverse events reported over 7 days of observation. A reduction of tumor burden was seen in three of five dogs treated. The reduction of tumor volume was correlated with Fas expression by the tumors, although one dog with a Fas-negative tumor survived for 82 weeks after treatment. Our data show that overexpression of FasL is suitable to promote apoptosis of Fas + melanomas, and support the notion that priming immune responder cells with apoptotic tumor cells may enhance antitumor responses. The results also suggest that intratumoral administration of FasL offers a safe route for therapeutic gene delivery.

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Section: Induction Of Apoptosis Of Canine Melanoma Cells By Faslsupporting

confidence: 86%

Section: Fasl Gene Deliverymentioning

confidence: 99%

Section: Induction Of Apoptosis Of Canine Melanoma Cells By Faslmentioning

confidence: 99%

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Enhancing antimelanoma immune responses through apoptosis

et al. 2003

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“…The molecular mechanisms underlying cell cycle regulation by p53 have been well defined. p53 transcriptionally up-regulates the p21WAF1 gene, the protein product of which inhibits the kinase activity of cdk4/cyclin D [49]. Activation of cdk4/cyclin D results in phosphorylation of pRb, release of pRb from the pRb/E2F/DP-1 complex, and progression to S phase via activation of E2F/DP-1 responsive genes [50].…”

Section: Discussionmentioning

confidence: 99%

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Ravera

Gioia

Andrea

et al. 2004

Experimental Cell Research

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Immunohistochemical analysis has demonstrated that the human IFI16 gene, in addition to the hematopoietic tissues, is highly expressed in endothelial cells and squamous stratified epithelia. In this study, we have developed a reliable HSV-derived replication-defective vector (TO-IFI16) to efficiently transduce IFI16 into primary human umbilical vein endothelial cells (HUVEC), which are usually poorly transfectable. HUVEC infection with TO-IFI16 virus suppressed endothelial migration, invasion and formation of capillary-like structures in vitro. In parallel, sustained IFI16 expression inhibited HUVEC cell cycle progression, accompanied by significant induction of p53, p21, and hypophosphorylated pRb. Further support for the involvement of these pathways in IFI16 activity came from the finding that infection with TO-IFI16 virus does not impair the in vitro angiogenic activity and cell cycle progression of HUVEC immortalized by HPV16 E6/E7 oncogenes, which are known to inactivate both p53 and pRb systems. This use of a reliable viral system for gene delivery into primary human endothelial cells assigns a potent angiostatic activity to an IFN-inducible gene, namely IFI16, and thus throws further light on antiangiogenic therapy employing IFNs. D

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“…The localization of p21 in the cytoplasmic or nuclear compartments of cells determines the effect of p21 on cellular proliferation, apoptosis, and oncogenic events (20). Studies (21,22) have demonstrated that in contrast to cytoplasmic p21, nuclear p21 inhibits cellular proliferation. Furthermore, these studies also demonstrated that although cytoplasmic p21 could interact with proliferating cell nuclear Ags, cyclin-dependent kinases, calmodulin, and cyclins, however, failed to exert an inhibitory effect on cell cycle.…”

Section: How Does Exogenous P21 Make Its Way To the Nucleus Of T Cell?mentioning

confidence: 99%

Recombinant p21 Protein Inhibits Lymphocyte Proliferation and Transcription Factors

Khanna

Plummer

Nilakantan

et al. 2005

The Journal of Immunology

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Cellular proliferation determines the events leading to the initiation and development of inflammation, immune activation, cancer, atherogenesis, and other disorders associated with aberrant cell proliferation. Cyclin inhibitor p21 plays a unique role in limiting cell cycle progression. However, its effectiveness can only be demonstrated with direct in vitro and in vivo delivery to control aberrant proliferation. We demonstrate that using a protein-transducing domain p21 protein a) localizes within the nuclear compartments of cells, b) interacts with transcription factors, NF-κB, and NFATs (NFATc and NFATp), and c) inhibits lymphocyte proliferation and expression of proinflammatory cytokines. This study using lymphocyte proliferation as a model suggests that the recombinant p21 protein can directly be delivered as a therapeutic protein to provide a novel, viable, and powerful strategy to limit proliferation, inflammation, alloimmune activation, cancer, and vascular proliferative disorders such as atherosclerosis.

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Sustained nuclear localization of p21/WAF-1 upon growth arrest induced by contact inhibition

Cited by 40 publications

References 29 publications

Enhancing antimelanoma immune responses through apoptosis

Enhancing antimelanoma immune responses through apoptosis

The interferon-inducible IFI16 gene inhibits tube morphogenesis and proliferation of primary, but not HPV16 E6/E7-immortalized human endothelial cells

Recombinant p21 Protein Inhibits Lymphocyte Proliferation and Transcription Factors

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