Downregulation of TNF-α and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor

Novak, Estela Maria; Metzger, Martin; Chammas, Roger; Costa, M. Da; Dantas, Kátia Cristina; Manabe, C.; Pires, Janaína Steger de Oliveira Costa; Oliveira, Aline Carlos de; Bydlowski, Sérgio Paulo

doi:10.1038/sj.gt.3302111

Cited by 32 publications

(30 citation statements)

References 42 publications

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“…Present data also clearly showed that RNA interference directed against Sp1 blocked the induction of VEGF, Cox2 and survivin by FSH, suggesting that Sp1 is a critical molecule in mediating FSH-induced angiogenesis. These results are consistent with previous studies of Sp1 involved in regulation of VEGF expression (33)(34)(35)(36)(37)(38).…”

Section: Discussionsupporting

confidence: 83%

The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

Lai

Zhang

et al. 2012

International Journal of Oncology

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Abstract. Previously, we demonstrated that follicle stimulating hormone (FSH) enhanced VEGF expression and facilitated ovarian cancer angiogenesis via the PI3K/AKT signaling pathway. In this study, we further investigated the involvement of microRNA-27a: ZBTB10-specificity protein pathway in the mechanism of FSH-induced VEGF, Cox2 and survivin expression. Treatment with FSH resulted in significant increase in the expression of VEGF, Cox2, survivin, Sp1 proteins and microRNA-27a in a dose-dependent manner, whereas reverse protein expression pattern was observed in ZBTB10. Downregulation of microRNA-27a using antisense microRNA27a blocked FSH-induced VEGF, Cox2 and survivin expression. Overexpression of ZBTB10 also attenuated the FSH-induced expression of these molecules. The enhanced expression of VEGF, Cox2 and survivin was also abolished by knocking down Sp1 using small interfering RNA. Collectively, these results indicated that stimulation of ovarian cancer cell VEGF, Cox2 and survivin expression by FSH involves the microRNA-27a: ZBTB10-specificity protein pathway. IntroductionOvarian cancer is the most lethal gynecological malignancy in women because of occult metastases within the peritoneal cavity and the advanced stage at detection when curative therapy is ineffective. Approximately 80-90% ovarian cancer is origin from ovarian surface epithelium. The etiology of ovarian epithelial cancer (OEC) remains to be clarified, multiple factors involved in OEC development, for example, hormonal, environmental and genetic factors may play a role. Currently, the gonadotropin theory of ovarian cancer proposes that elevated serum gonadotropins, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), contribute significantly to the development of ovarian cancer. In previous study, Choi et al have reported that FSH enhanced ovarian cancer cells proliferation and invasion by PI3K/AKT signal pathway (1,2). Recent study in our laboratory demonstrated that FSH inhibits ovarian cancer cell apoptosis by upregulating survivin and downregulating PDCD6 and DR5 (3). These studies indicate FSH plays an important role in OEC occurrence, especially in postmenopausal women. In our previous work, it was also reported that activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma (4). This study also showed that survivin and HIF1α are involved in FSH-mediated VEGF expression by PI3K/ AKT signal pathway. Survivin is a member of the inhibitor of apoptosis protein (IAP) family, in addition to the anti-apoptosis function, the role of survivin to regulate VEGF expression has been described in various tumor cell types (5,6). These factors contribute to tumor angiogenesis. Inflammation also facilitate tumor angiogenesis, Cox2 is an important effector molecule of inflammation and was reported to be involve in VEGF expression and tumor angiogenesis. In our recent study, it was found FSH could significantly upregulate Cox2 expression in a dose-dependent manner (unpublish data). Althoug...

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Section: Discussionsupporting

confidence: 83%

The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

Lai

Zhang

et al. 2012

International Journal of Oncology

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“…Vascular endothelial growth factors (VEGFs), epidermal growth factors (EGFs), platelet-derived endothelial cell growth factors (PDGFs), and acidic and basic fibroblast growth factors (aFGFs and bFGFs) are major angiogenic mediators as well as strong vascular permeability factors (Chiba et al 2008;Li et al 2005). Moreover, tumor cells release several pro-angiogenic factors that enhance metastasis, and therefore, shorten survival in tumor-bearing hosts (Novak et al 2003). TSU-68 significantly inhibits tumor growth and liver metastasis from human colon cancer xenografts through inhibition of VEGF, bFGF, and PDGF-mediated angiogenic activity, which could be useful during the treatment of colon cancer (Yorozuya et al 2005).…”

Section: Introductionmentioning

confidence: 98%

Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect

et al. 2009

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“…These oligonucleotides act as competitive binding sites for the specific transcription factor, preventing it from binding to its consensus binding sites within the promoters of genes, thus inhibiting its function. This technology has been applied effectively in cell culture and mouse models to inhibit the activity of NFK , E2F, Stat1, Sp1 and AP-1 [63][64][65][66][67]. The treatment of oral squamous cell carcinoma cells with AP-1 decoys interferes with the invasive ability of these cells [68].…”

Section: Current Technologies As Potential Therapeutics Against mentioning

confidence: 98%

Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target

Leaner¹,

Donninger²,

Birrer³

2007

CCTR

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The field of cancer therapy is rapidly moving forward with the development of numerous prospective new agents designed to inhibit cellular factors involved in signal transduction, cell proliferation, and the onset of apoptosis. At the core of these biological processes are transcription factors that are the functional mediators of these effects. Transcription factors are the downstream targets of numerous signal transduction pathways that are central to the process of carcinogenesis. The Activator Protein-1 (AP-1) complex is one such factor that has a central role in multiple processes involved in tumorigenesis including proliferation, migration, invasion and metastasis. The focus of this review is, using AP-1 as a model, to discuss transcription factors as targets for cancer therapy. The feasibility of targeted disruption of AP-1 by various agents such as dominant-negative mutants, small molecule inhibitors, transcription factor decoys (TFD), chemotherapeutic drugs, chemoprevention agents, siRNA and natural products will be explored.

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Downregulation of TNF-α and VEGF expression by Sp1 decoy oligodeoxynucleotides in mouse melanoma tumor

Cited by 32 publications

References 42 publications

The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

The microRNA-27a: ZBTB10-specificity protein pathway is involved in follicle stimulating hormone-induced VEGF, Cox2 and survivin expression in ovarian epithelial cancer cells

Norcantharidin is a small-molecule synthetic compound with anti-angiogenesis effect

Transcription Factors as Targets for Cancer Therapy: AP-1 a Potential Therapeutic Target

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