Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression

Zhang, G; Luo, Xiao; Sumithran, Eric; Pua, Vernon Sc; Barnetson, R S; Halliday, Gary M.; Khachigian, Levon M.

doi:10.1038/sj.onc.1209726

Cited by 56 publications

(46 citation statements)

References 35 publications

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“…Immunohistochemical staining of JUN protein on sections of paraffin-embedded human BCC samples confirmed qRT-PCR results (Figure 2b). Strong and specific nuclear staining was found throughout the tumor islands pointing to transcriptionally active JUN protein in accordance with previous studies (Zhang et al, 2006). No staining was found in the surrounding stroma.…”

Section: Jun Expression Is Increased In Response To Gli In Human Kerasupporting

confidence: 92%

Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes

et al. 2009

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Sustained Hedgehog (HH) signaling is implicated in basal cell carcinoma of the skin and other types of cancer. Here we show that GLI1 and GLI2, the main transcriptional activators of the HH pathway, directly regulate expression of the activator protein 1 (AP-1) family member JUN, a transcription factor controlling keratinocyte proliferation and skin homeostasis. Activation of the JUN promoter by GLI is dependent on a GLI-binding site and the AP-1 sites known to be involved in self-activation of JUN. Transcription of JUN is greatly enhanced in the presence of GLI and requires activated JUN protein.GLI2act is a more potent activator than GLI1 in these experiments and physical interaction with phosphorylated JUN was only detected for GLI2act. The synergistic effect of GLI and JUN extends to the activation of further GLI target genes as shown by shRNA-mediated knockdown of JUN in human keratinocytes. Some of these cooperatively activated genes are involved in cell-cycle progression, which is consistent with a significant reduction of the proliferative potential of GLI in the absence of JUN. These results suggest a novel connection between HH/GLI pathway activity and JUN, which may contribute to the oncogenic activity of HH/GLI signaling in skin.

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Section: Jun Expression Is Increased In Response To Gli In Human Kerasupporting

confidence: 92%

Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes

et al. 2009

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“…These findings indicate that DNAzymes to this transcription factor may potentially be useful as inhibitors of cutaneous carcinoma. 44 This DNAzyme also inhibited VEGF-induced neovascularization in the rat cornea and solid melanoma growth in mice. 5 DNAzyme targeting a specific motif in the 5 0 untranslated region of Egr-1 mRNA blocked angiogenesis in subcutaneous Matrigel plugs in mice and inhibited xenografted MCF-7 human breast carcinoma growth in nude mice.…”

Section: Discussionmentioning

confidence: 92%

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

et al. 2009

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Previously, we designed a DNAzyme (b1DE) targeting the human b1 integrin subunit, which efficiently digested the mRNA of the b1 integrin subunit and downregulated b1 integrin expression in endothelial cells. This DNAzyme blocked the adhesion of endothelial cells and abolished their ability to form microcapillary tubes in Matrigel. In our present study, we demonstrate that b1DE effectively inhibited neovascularization in Matrigel plugs (BALB/c mice, n ¼ 20) and solid human carcinoma tumors developed in nude mice (BALB/cA nude (nu-/-)-B6.Cg-Foxn1 nu ) (n ¼ 30) using prostate carcinoma cells PC-3 (n ¼ 15) and colon adenocarcinoma cells CX1.1 (n ¼ 15). When injected intratumorally, it significantly reduced the tumor size and number of microvessels developed by both CX1.1 and PC-3 cells within the 3 weeks of experiment duration. Thus, DNAzymes targeting b1 integrin genes can inhibit multiple key tumorigenic processes in vitro and in vivo and may serve as useful anti-cancer agents.

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“…DzF also inhibited both cellular migration (40%) and chemoinvasion (60%) in these cells. DzF was also capable of significantly reducing s.c. tumor growth when We have also more recently shown that the Dz13 DNAzyme is capable of reducing not only solid melanoma growth, but squamous cell carcinoma growth in mice as well (47). Dz13 down-regulated c-Jun expression in T79 cells and also inhibited their growth in a dose-dependent manner.…”

Section: Dnazymes As Antineoplastic Agents In Vivomentioning

confidence: 95%

DNAzyme technology and cancer therapy: cleave and let die

Dass

Choong

Khachigian

2008

Molecular Cancer Therapeutics

128

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Squamous cell carcinoma growth in mice and in culture is regulated by c-Jun and its control of matrix metalloproteinase-2 and -9 expression

Cited by 56 publications

References 35 publications

Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes

Cooperation between GLI and JUN enhances transcription of JUN and selected GLI target genes

DNAzymes to mouse β1 integrin mRNA in vivo: targeting the tumor vasculature and retarding cancer growth

DNAzyme technology and cancer therapy: cleave and let die

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