C-Myc Is a Critical Mediator of the Phenotypes of <i>Apc</i> Loss in the Intestine

Wilkins, Julie; Sansom, Owen J.

doi:10.1158/0008-5472.can-07-5558

Cited by 58 publications

(55 citation statements)

References 31 publications

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“…There has been much debate over whether c-Myc is a therapeutic target for colorectal cancer and the difficulties regarding targeting c-Myc using small molecules (Soucek et al, 2008;Wilkins and Sansom, 2008). Our study here suggests that reduction of c-Myc (as well as complete ablation) may be a rationale for chemoprevention of colorectal cancer.…”

mentioning

confidence: 71%

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Athineos

Sansom

2010

Oncogene

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confidence: 71%

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Athineos

Sansom

2010

Oncogene

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“…Moreover, we also found that RNAi-mediated downregulation of RCK/p54 expression could significantly reduce the Tcf transcriptional activity and the expression levels of the known Wnt target gene such as β-catenin, c-Myc, cyclinD1, cox-2, Livin, survivin and VEGF. [26][27][28][29][30][31][32] Thus, we conclude that the overexpression of RCK/p54 takes part in the activation of Wnt signaling pathway and transmits the canonical Wnt signals to downstream molecules despite the presence of APC mutation, which seem to be compatible with the "just right" chemically synthesized (BioAsia bioengineering Inc., Shanghai, China) and then annealed to form double-stranded cDNA fragments that were inserted between the BamHI and HindIII sites of linearized pSilencer4.1-CMVneo vector (Ambion, USA) downstream of CMV promoter according to the manufacturer's instructions ( Fig. 2A).…”

Section: Methodsmentioning

confidence: 99%

Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo

Lin¹,

Wang²,

Shen³

et al. 2008

Cancer Biology & Therapy

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Colorectal cancer is the third most common cancer in both men and women around the world. Although much progress of the mechanism of colorectal carcinogenesis has been made, the studies centering on the mechanisms of tumorigenesis are much needed to be further exploited. The overexpression of RCK/p54 gene, a member of the DEAD box protein/RNA helicase family, has been found in this malignancy. Roles of RCK in the development of colon cancer, however, are unknown. In this report, we explored whether RCK/p54 plays a role in maintaining the malignant phenotype and functions in the canonical Wnt signaling pathway of colorectal cancer cells harboring an APC mutation. The ectopic overexpression of RCK/p54 gene in colorectal cancer cells by transfection with RCK/p54 cDNA could lead to a significant increase of Tcf transcriptional activity and expression levels of Wnt target genes. By RNAi assay, we also observed that the Tcf transcriptional activity in LoVo-shRNA cells was significantly decreased by approximately 61.3%, while the mRNA and protein expression levels of Wnt target genes were also obviously decreased. Furthermore, the anti-tumour effects and its possible mechanisms of actions in LoVo cells elicited by a decrease in the level of RCK/ p54 by RNAi were examined. Results showed that RCK/p54 downregulation could significantly reduce the viability of LoVo cells, increased cell number of S phase, led to cell apoptosis induction, and inhibited tumor growth in nude mice. Taken together, RCK/ p54 might be a determinant of colorectal cancer proliferation by activating the canonical Wnt pathway and RCK/p54-shRNA might be a potential strategy for colorectal cancer gene therapy.

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“…c-myc is believed to participate in most aspects of cellular function, including replication, growth, metabolism, differentiation, and apoptosis [6][7][8]. A frequent genetic abnormality seen in colon cancer is the elevated expression of c-myc [4,9]. The importance of c-myc expression in colon cancer has been demonstrated in both studies of transgenic mice and clinical research [10,11].…”

Section: Introductionmentioning

confidence: 99%

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

Zhang

Tian

2009

Cellular and Molecular Biology Letters

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Abstract:We investigated the effects of RNA interference-mediated silencing of the c-myc gene on celluar proliferation and apoptosis in human colon cancer HT-29 cells in vitro and in vivo. A small interfering RNA (siRNA) targeting c-myc was designed, the DNA template was synthesized, and the siRNA was obtained by in vitro transcription. After siRNA transfection into HT-29 and human neuroblastoma IMR-32 cells with Lipofectamine 2000 TM , the proliferation of the HT-29 and IMR-32 cells was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and Hoechst 33258 staining was used to observe cell apoptosis. Following gene transfer to HT-29 cells, the expression of c-myc mRNA was examined via reverse transcription polymerase chain reaction, and the level of the protein via Western blot assay. Growth curves were constructed and in vivo experiments were performed on nude mice to assess the effects of c-myc silencing on tumor growth. The c-myc expression in the tumor tissue was measured by reverse transcription polymerase chain reaction and subsequently by immunohistochemistry. Our paper demonstrates that the delivery of siRNA directed against c-myc not only efficiently down-regulated the expression of c-myc, inhibited the proliferation of HT-29 cells and induced apoptosis in vitro, but also suppressed the growth of colon cancer cells in vivo.

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C-Myc Is a Critical Mediator of the Phenotypes of Apc Loss in the Intestine

Cited by 58 publications

References 31 publications

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Myc heterozygosity attenuates the phenotypes of APC deficiency in the small intestine

Knockdown of RCK/p54 expression by RNAi inhibits proliferation of human colorectal cancer cells in vitro and in vivo

The knockdown of c-myc expression by RNAi inhibits cell proliferation in human colon cancer HT-29 cells in vitro and in vivo

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