Control of VEGF Expression in Triple-Negative Breast Carcinoma Cells by Suppression of <i>SAF-1</i> Transcription Factor Activity

Ray, Alpana; Dhar, Srijita; Ray, Bimal K.

doi:10.1158/1541-7786.mcr-10-0598

Cited by 29 publications

(37 citation statements)

References 51 publications

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“…Ray et al (31) recently showed that MAZ can induce the transcriptional activation of VEGF in breast cancer cells. In line with these results, we observed that MAZ knockdown significantly reduced VEGF mRNA expression in hCMEC/D3 cells ( Fig .…”

Section: Resultsmentioning

confidence: 99%

Myc‐associated zinc finger protein (MAZ) is regulated by miR‐125b and mediates VEGF‐induced angiogenesis in glioblastoma

et al. 2012

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In patients with glioblastomas, vascular endothelial growth factor (VEGF) is a key mediator of tumor-associated angiogenesis. Glioblastomas are notorious for their capacity to induce neovascularization, driving continued tumor growth. Here we report that miR-125b is down-regulated in glioblastoma-associated endothelial cells, resulting in increased expression of its target, myc-associated zinc finger protein (MAZ), a transcription factor that regulates VEGF. The down-regulation of miR-125b was also observed on exposure of endothelial cells to glioblastoma-conditioned medium or VEGF, resulting in increased MAZ expression. Further analysis revealed that inhibition of MAZ accumulation by miR-125b, or by MAZ-specific shRNAs, attenuated primary human brain endothelial cell migration and tubule formation in vitro, phenomena considered to mimick angiogenic processes in vitro. Moreover, MAZ expression was elevated in brain blood vessels of glioblastoma patients. Altogether these results demonstrate a functional feed-forward loop in glioblastoma-related angiogenesis, in which VEGF inhibits the expression of miR-125b, resulting in increased expression of MAZ, which in its turn causes transcriptional activation of VEGF. This loop is functionally impeded by the VEGF receptor inhibitor vandetanib, and our results may contribute to the further development of inhibitors of tumor-angiogenesis.

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Section: Resultsmentioning

confidence: 99%

Myc‐associated zinc finger protein (MAZ) is regulated by miR‐125b and mediates VEGF‐induced angiogenesis in glioblastoma

et al. 2012

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“…MAZ is a zinc finger transcription factor that binds to GpCrich cis-elements in the promoter regions of numerous mammalian genes and is also able to recruit different proteins, such as methylases and acetylases, to the transcriptional complex, thereby acting as an initiator or terminator of transcription. 31 The transcription factor has been implicated in VEGF-induced angiogenesis 16,32,33 ; this effect being negatively controlled by microRNA-125b, of which MAZ is an inhibitory target. 16 Of note, we found that the expression of microRNA-125b in SV-APCs is inversely correlated with their ability to induce reparative vascularization in the mouse LI model.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Profile of Human Adventitial Progenitor Cells Correlates With Therapeutic Outcomes in a Mouse Model of Limb Ischemia

Gubernator

Slater

Spencer

et al. 2015

ATVB

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Objective— We investigated the association between the functional, epigenetic, and expressional profile of human adventitial progenitor cells (APCs) and therapeutic activity in a model of limb ischemia. Approach and Results— Antigenic and functional features were analyzed throughout passaging in 15 saphenous vein (SV)–derived APC lines, of which 10 from SV leftovers of coronary artery bypass graft surgery and 5 from varicose SV removal. Moreover, 5 SV-APC lines were transplanted (8×10 5 cells, IM) in mice with limb ischemia. Blood flow and capillary and arteriole density were correlated with functional characteristics and DNA methylation/expressional markers of transplanted cells. We report successful expansion of tested lines, which reached the therapeutic target of 30 to 50 million cells in ≈10 weeks. Typical antigenic profile, viability, and migratory and proangiogenic activities were conserved through passaging, with low levels of replicative senescence. In vivo, SV-APC transplantation improved blood flow recovery and revascularization of ischemic limbs. Whole genome screening showed an association between DNA methylation at the promoter or gene body level and microvascular density and to a lesser extent with blood flow recovery. Expressional studies highlighted the implication of an angiogenic network centered on the vascular endothelial growth factor receptor as a predictor of microvascular outcomes. FLT-1 gene silencing in SV-APCs remarkably reduced their ability to form tubes in vitro and support tube formation by human umbilical vein endothelial cells, thus confirming the importance of this signaling in SV-APC angiogenic function. Conclusions— DNA methylation landscape illustrates different therapeutic activities of human APCs. Epigenetic screening may help identify determinants of therapeutic vasculogenesis in ischemic disease.

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“…56 Increases in serum SAA correlate with carcinogenesis and neoplastic progression; SAA is proposed as a biomarker for a variety of human cancers, 56 including lung, 57 colorectal 58 , renal, 59 ovarian, 60 and breast cancer. 61 The SAA gene is induced by IL-6 when stimulated with proinflammatory cytokines. 62 SAA is also regulated by an activating factor (SAF-1) that is linked to VEGF expression and angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Senescence-associated-gene signature identifies genes linked to age, prognosis, and progression of human gliomas

Coppola

Balducci

Chen

et al. 2014

Journal of Geriatric Oncology

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Control of VEGF Expression in Triple-Negative Breast Carcinoma Cells by Suppression of SAF-1 Transcription Factor Activity

Abstract: Angiogenesis plays a significant role in cancer by providing increased blood supply to the affected tissues and thus bringing in growth factors, cytokines, and various nutrients for tumor growth.

Cited by 29 publications

References 51 publications

Myc‐associated zinc finger protein (MAZ) is regulated by miR‐125b and mediates VEGF‐induced angiogenesis in glioblastoma

Myc‐associated zinc finger protein (MAZ) is regulated by miR‐125b and mediates VEGF‐induced angiogenesis in glioblastoma

Epigenetic Profile of Human Adventitial Progenitor Cells Correlates With Therapeutic Outcomes in a Mouse Model of Limb Ischemia

Senescence-associated-gene signature identifies genes linked to age, prognosis, and progression of human gliomas

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