β-Catenin Antisense Treatment Decreases β-Catenin Expression and Tumor Growth Rate in Colon Carcinoma Xenografts

Green, Douglas W.; Roh, Haeri; Pippin, James A.; Drebin, Jeffrey A.

doi:10.1006/jsre.2001.6241

Cited by 65 publications

(42 citation statements)

References 15 publications

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“…Overexpression of similar ␤-catenin mutants leads to neoplastic transformation of E1A-immortalized epithelial cells and stimulated proliferation of p53-or ARF-null mouse embryo fibroblasts (36,37). Consistent with these results, specific reduction of ␤-catenin in APC-mutant colon cancer cells by antisense oligonucleotides or small interference RNA inhibited the proliferation, anchorage-independent growth, and cellular invasiveness in vitro and neoplastic growth of xenografts in animals (27,28,38). In keeping with the role of ␤-catenin in cell growth, activation of the RXRmediated pathway reduced cell proliferation (Fig.…”

Section: Discussionmentioning

confidence: 63%

Adenomatous Polyposis Coli (APC)-independent Regulation of β-Catenin Degradation via a Retinoid X Receptor-mediated Pathway

Xiao

Ghosn

Hinchman

et al. 2003

Journal of Biological Chemistry

139

147

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␤-catenin is a component of stable cell adherent complexes whereas its free form functions as a transcription factor that regulate genes involved in oncogenesis and metastasis. Free ␤-catenin is eliminated by two adenomatous polyposis coli (APC)-dependent proteasomal degradation pathways regulated by glycogen synthase kinase 3␤ (GSK3␤) or p53-inducible Siah-1. Dysregulation of ␤-catenin turnover consequent to mutations in critical genes of the APC-dependent pathways is implicated in cancers such as colorectal cancer. We have identified a novel retinoid X receptor (RXR)-mediated APC-independent pathway in the regulation of ␤-catenin. In this proteasomal pathway, RXR agonists induce degradation of ␤-catenin and RXR␣ and repress ␤-catenin-mediated transcription. In vivo, ␤-catenin interacts with RXR␣ in the absence of ligand, but RXR agonists enhanced the interaction. RXR agonist action was not impaired by GSK3␤ inhibitors or deletion of the GSK3␤-targeted sequence from ␤-catenin. In APC-and p53-mutated colorectal cancer cells, RXR agonists still inactivated endogenous ␤-catenin via RXR␣. Interestingly, deletion of the RXR␣ A/B region abolished ligand-induced ␤-catenin degradation but not RXR␣-mediated transactivation. RXR␣-mediated inactivation of oncogenic ␤-catenin paralleled a reduction in cell proliferation. These results suggest a potential role for RXR and its agonists in the regulation of ␤-catenin turnover and related biological events.

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Section: Discussionmentioning

confidence: 63%

Adenomatous Polyposis Coli (APC)-independent Regulation of β-Catenin Degradation via a Retinoid X Receptor-mediated Pathway

Xiao

Ghosn

Hinchman

et al. 2003

Journal of Biological Chemistry

139

147

View full text Add to dashboard Cite

show abstract

“…The significance of these observations remains to be elucidated in a larger study. There is an obvious need to identify novel molecular targets for cancer therapeutics, and in this respect, the recent data showing that suppression of β-catenin can inhibit the neoplastic growth of APCmutant colorectal cancer are of interest [25] . The correlation between β-catenin expression pattern and clinical outcome is a controversial subject.…”

Section: Discussionmentioning

confidence: 99%

Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

Elzagheid

Buhmeida²,

Korkeila³

et al. 2008

WJG

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AIM:To investigate the changing pattern of β-catenin expression and its prognostic value in advanced colorectal cancer (CRC). METHODS: Archival tumor samples were analyzed for β-catenin using immunohistochemistry (IHC) in 95 patients with advanced CRC. RESULTS: Membranous β-catenin expression was found in the normal colorectal epithelium. Almost 1 0 0 % o f C R C c a s e s s h o w e d m e m b ra n o u s a n d cytoplasmic expression, and 55 (58%) cases showed nuclear expression. In univariate (Kaplan-Meier) survival analysis, only the nuclear index (NI) was a significant predictor of disease-free survival (DFS) (P = 0.023; n = 35), with a NI above the median associated with longer DFS (34.2 mo) than those with a NI below the median (15.5 mo) (P = 0.045, ANOVA). The other indices were not significant predictors of DFS, and none of the three tested indices (for membranous, cytoplasmic, or nuclear expression) predicted diseasespecific survival (DSS). However, when dichotomized as positive or negative nuclear expression, the former was a significant predictor of more favorable DFS (P = 0.041) and DSS (P = 0.046). CONCLUSION: Nuclear β-catenin expression provides additional information in predicting patient outcome in advanced CRC.

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“…ESCC in Western countries, where it is relatively uncommon, shares the above-mentioned characteristics except that tumors are rather frequent in the lower esophagus [5,6] . Beta-catenin is involved in the ubiquitin/proteasomedependent protein degradation pathway, which plays an essential role in controlling the levels of various cellular proteins and therefore regulates basic cellular processes such as cell cycle progression, signal transduction, and cell transformation [17] . We examined beta-catenin expression at the mRNA level by reverse transcription-PCR.…”

Section: Discussionmentioning

confidence: 99%

Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

Cao²,

Wang³

et al. 2007

WJG

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AIM:To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma (ESCC).METHODS: Beta-catenin mRNA expression level in 40 ESCC patients (28 males and 12 females, age range 38-82 years, median 60 years) was analyzed by realtime PCR. Beta-catenin mRNA expression levels in tumor cells were categorized as weaker (level 1) or equal to or stronger (level 2) than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS:Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis (0.0776 ± 0.0369 vs 0.3413 ± 0.1803, P < 0.001) and deeper tumor invasion (0.0751 ± 0.0356 vs 0.3667 ± 0.1928, P < 0.001), and a poorer survival rate (P = 0.0024) than ESCC with level 1 expression. CONCLUSION:Beta-catenin expression in ESCC is of great importance.

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β-Catenin Antisense Treatment Decreases β-Catenin Expression and Tumor Growth Rate in Colon Carcinoma Xenografts

Cited by 65 publications

References 15 publications

Adenomatous Polyposis Coli (APC)-independent Regulation of β-Catenin Degradation via a Retinoid X Receptor-mediated Pathway

Adenomatous Polyposis Coli (APC)-independent Regulation of β-Catenin Degradation via a Retinoid X Receptor-mediated Pathway

Nuclear β-catenin expression as a prognostic factor in advanced colorectal carcinoma

Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

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