Somatic APC Inactivation Mechanisms in Sporadic Colorectal Cancer Cases in Hungary

Kámory, Enikő; Olasz, Judit; Csuka, Orsolya

doi:10.1007/s12253-008-9019-y

Cited by 11 publications

(7 citation statements)

References 31 publications

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“…However, the prognosis of CRC patients and the correlation between epigenetic changes in 5-FU adjuvant chemotherapy remain controversial (de Vos tot Nederveen Cappel et al, 2004;Crozier et al, 2006;Hasegawa et al, 2006). On the other hand, a relatively higher frequency of APC (germline or somatic) mutations in sporadic CRC has been reported in other ethnic groups (Esteller et al, 2000;Fearnhead et al, 2001;Kámory et al, 2008). However, a lower germline APC mutation frequency in Taiwanese CRC patients is relatively unique (Chen et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

The Association of Methylation in the Promoter of APC and MGMT and the Prognosis of Taiwanese CRC Patients

Chen

Chiu

et al. 2009

Genetic Testing and Molecular Biomarkers

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Section: Introductionmentioning

confidence: 99%

The Association of Methylation in the Promoter of APC and MGMT and the Prognosis of Taiwanese CRC Patients

Chen

Chiu

et al. 2009

Genetic Testing and Molecular Biomarkers

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“…6,7 APC mutations mostly induced the deletion of the C-terminal half of the protein which led to the failure to assemble a functional destruction complex, which ultimately results in the constitutive stabilization of β-catenin. 8,9 Some studies have reported that the co-overexpression of RCK/p54 and c-Myc was correlated with malignant transformation accompanying with inactivation of anti-oncogenes including APC and K-ras, which leads to transcriptional activation of c-Myc expression through the β-catenin/Tcf-4 complex. 10,11 The role of RCK/p54 in colorectal cancer has been examined in some researches; however, specifically reducing its level by genetic means in established colorectal cancer cell lines is still helpful for a better understanding of its role in maintaining the malignant phenotype, particularily association with activation of the Wnt signaling pathway during the colorectal carcinogenesis.…”

Section: Introductionmentioning

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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“…However, it is impossible to point out exact mutation site and mutation type (Orita et al, 1989). Genital cell mutation of APC gene is Molecular pathology foundation of Familial Adenomatous Polyposis (FAP), meanwhile somatic mutation plays an important role to cause sporadic rectal cancer (Kámory et al, 2008;Kittiyod Poovorawan et al, 2012). Most of somatic mutation is nonsense mutation, and more than 60% of somatic mutation called codon 1286~1513, whose area is named MCR (Tang et al, 2006;Hinoi et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Significance of HPV Infection and Genic Mutation of APC and K-ras in Patients with Rectal Cancer

Sun

Wang²,

Zhao³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: Significance of HPV infection and genic mutation of APC and K-ras in rectal cancer has been investigated but not clarified. The objective of our study was to investigate these parameters in patients with rectal cancer to analyze correlations with biological behaviour, to determine relationships among the three, and also to demonstrate survival prognosis effects. Methods: From December 2007 to September 2008, 75 rectal cancer cases confirmed by histopathology in the Tumor Hospital of Xinjiang Medical University were enrolled. The control group consisted of normal rectal mucous membrane taken simultaneously, a least 10 cm distant from the carcinoma fringe. HPV DNA, the MCR of APC and exon-1 of K-ras were detected by PCR and PCR-SSCP. All results were analyzed in relation to clinical pathological material, using chi-square and correlation analysis via SPSS.13 and Fisher's Exact Probability via STATA. 9.0. All 75 patients were followed up for survival analysis using Kaplan-Meier and Log-rank tests. Results: 55 out of 75 cases demonstrated gene HPV L1 while it was notdetected in normal rectal mucosa tissue. HPV infection was correlated with age and lymphatic metastasis (P<0.05) but not other characteristics, such as ethnicity, tumor size, histological type, tumor type, Duke's stage and infiltration depth. Some 43 cases exhibited APC genic mutation (57.3%) and 34 K-ras genic mutation (45.3%). APC genic mutation was correlated with gender( P<0.05), but not age, histological type, infiltration depth, lymphatic metastasis and Duke's stage. In 55 cases of rectal cancer with HPV infection, there were 31 cases with genic mutation of APC (56.4%) and 24 with genic mutation of K-ras (43.6%). For the 20 cases of rectal cancer with non-HPV infection, the figures were 12 cases (60%) and 10 (50.0%), respectively, with no significant relation. Survival analysis showed no statistical significance for K-ras genic mutation, APC genic mutation or HPV infection (P>0.05). However, the survival time of the patients with HPV infection was a little shorter than in cases without HPV infection. Conclusions: Our results suggest that HPV infection might be an important factor to bring about malignant phenotype of rectal cancer and influence prognosis. Genic mutation of APC and K-ras might be common early molecular events of rectal cancer, but without prognostic effects on medium-term or early stage patients with rectal cancer.

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Somatic APC Inactivation Mechanisms in Sporadic Colorectal Cancer Cases in Hungary

Cited by 11 publications

References 31 publications

The Association of Methylation in the Promoter of APC and MGMT and the Prognosis of Taiwanese CRC Patients

The Association of Methylation in the Promoter of APC and MGMT and the Prognosis of Taiwanese CRC Patients

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

Significance of HPV Infection and Genic Mutation of APC and K-ras in Patients with Rectal Cancer

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