Raf and VEGF: emerging therapeutic targets in Kaposi's sarcoma-associated herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic tumors

Hamden, Khalief E.; Whitman, Audy G.; Ford, Patrick W.; Shelton, John G.; McCubrey, James A.; Akula, Shaw M.

doi:10.1038/sj.leu.2403532

Cited by 36 publications

(28 citation statements)

References 91 publications

(131 reference statements)

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“…FGF-2, VEGF, and VEGFR-1 appear to have an equivalent distribution in corresponding CCS structures, and this finding agrees with the known autocrine and paracrine roles of the two factors and their synergic induction of angiogenesis (Costa et al, 2004;Hamden et al, 2005;Bikfalvi et al, 1997). Of particular interest is the finding that VEGF and VEGFR-1 are expressed at the level of the same territory.…”

Section: Filopodia and Angiogenic Signalssupporting

confidence: 78%

Tubular sprouting as a mode of vascular formation in a colonial ascidian (tunicata)

Gasparini

Longo

Manni

et al. 2007

Developmental Dynamics

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Section: Filopodia and Angiogenic Signalssupporting

confidence: 78%

Tubular sprouting as a mode of vascular formation in a colonial ascidian (tunicata)

Gasparini

Longo

Manni

et al. 2007

Developmental Dynamics

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“…PD98059 is a commonly used small molecule inhibitor that inhibits both the phosphorylation and activation of MEK. 18 We found PD98059 to significantly lower phosphorylation of ERK1/2 in HFF, BCBL-1, BC-1, BC-2, BCP-1, and BJAB cells ( Figure 1C). PD98059 treatment lowered ERK1/2 phosphorylation in a dosedependent manner but did not lower the level of total ERK1/2 ( Figure 1C).…”

mentioning

confidence: 88%

B-Raf–dependent expression of vascular endothelial growth factor–A in Kaposi sarcoma–associated herpesvirus-infected human B cells

Akula

Ford

Whitman

et al. 2005

Blood

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IntroductionKaposi sarcoma-associated herpesvirus/human herpesvirus 8 (KSHV/HHV-8) is the latest addition to the list of human herpesviruses. KSHV was first isolated from Kaposi sarcoma (KS) lesions in persons suffering from acquired immunodeficiency syndrome (AIDS) in 1994. 1 The cancerous conditions that are etiologically associated with KSHV are KS, primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). 2 Apart from the inflammatory cytokines (ICs)/growth factors (GFs), lytic KSHV infection plays an instrumental role in the progression of KS lesions. 3 The lytic cycle of infection is also critical for the spread of KSHV to different organs. Successful KSHV infection is characterized by both virus entry and the ability of the virus to establish latency.In our earlier study, we provided evidence to show that the overexpression of Raf specifically enhanced KSHV infection of target cells at the level of entry. 4 Regulation of Raf is crucial for the proper maintenance of cell growth, proliferation, apoptosis, and differentiation. 5 Of the 3 isoforms, B-Raf has gained a lot of focus over the last couple of years due to the detection of B-Raf somatic missense mutations in malignant melanomas (66%), colon cancers (15%), and at lower frequencies in a wide variety of human cancers. [6][7][8] The ability of Raf to regulate vascular endothelial growth factor-A (VEGF-A) has also been demonstrated. 4 In separate studies, we found VEGF-A to enhance KSHV infection of fibroblasts and epithelial cells. 9,10 Interestingly, constitutive activation of the components (Ras/Raf) of the mitogen-activated protein kinase (MAPK) pathway of signaling as well as VEGF expression has been a common feature with KSHV pathogenesis. 11,12 Hence, in this study we attempted to analyze the relationship between the expression of B-Raf and VEGF-A in KSHV-infected hematopoietic cells. We provide evidences for the existence of a Raf-dependent VEGF-A expression in KSHV-infected hematopoietic cells. Materials and methods Cell cultureHuman foreskin fibroblasts (HFFs; Clonetics, Walkersville, MD), BCBL-1, BC-1 (American Type Culture Collection [ATCC], Manassas, VA; CRL-2230), BC-2 (ATCC CRL-223), BCP-1 (ATCC CRL-2294), and BJAB cells were used in this study. Target cells were grown in either phenol red-free Dulbecco modified Eagle medium (DMEM) or RPMI medium (Invitrogen, Carlsbad, CA) containing 10% charcoal-stripped fetal bovine serum (FBS; Atlanta Biologicals, Lawrenceville, GA), L-glutamine, and antibiotics. 13,14 Dermal microvascular endothelial cells (HMVEC-Ds; CC-2543; Clonetics) were propagated in EGM MV-microvascular endothelial cell medium (Clonetics) as per standard protocols. 13 The passage numbers for HFFs and HMVEC-Ds used in this study ranged between 6 and 10, and 5 and 9, respectively. HFF/pBabePuro3, HFF/⌬B-Raf [DD] :ER, and HFF/⌬B-Raf [FF] : ER cells were cultured as per standard protocols. 4,10 ␤-Estradiol (1 M) stimulation of these cells results in the activation of ⌬B-Raf:ER fusion proteins. 4Inhibitors PD98059 w...

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“…Liu et al 57 provided further evidence that VEGF is a critical mediator of angiogenesis stimulation by vIL-6 in vitro and in vivo. Hamden et al 58 showed that Raf regulates the expression of a variety of growth factors including VEGF. On the other hand, Wang et al 59 demonstrated that K1, the transmembrane glycoprotein that is encoded by the first open reading frame of KSHV, is responsible of the VEGF upregulation mediated at the transcriptional level by VEGF promoter activation.…”

Section: Discussionmentioning

confidence: 99%

KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent angiogenesis and establish functional gap junctions with endothelial cells

et al. 2007

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Raf and VEGF: emerging therapeutic targets in Kaposi's sarcoma-associated herpesvirus infection and angiogenesis in hematopoietic and nonhematopoietic tumors

Cited by 36 publications

References 91 publications

Tubular sprouting as a mode of vascular formation in a colonial ascidian (tunicata)

Tubular sprouting as a mode of vascular formation in a colonial ascidian (tunicata)

B-Raf–dependent expression of vascular endothelial growth factor–A in Kaposi sarcoma–associated herpesvirus-infected human B cells

KSHV-transformed primary effusion lymphoma cells induce a VEGF-dependent angiogenesis and establish functional gap junctions with endothelial cells

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