Correlations of partial and extensive methylation at the p14ARF locus with reduced mRNA expression in colorectal cancer cell lines and clinicopathological features in primary tumors

Zheng, Shichun; Chen, Pengchin; McMillan, Alex; Lafuente, Amàlia; Lafuente, María José; Ballesta, Antonio M.; Trías, Manuel; Wiencke, John K.

doi:10.1093/carcin/21.11.2057

Cited by 79 publications

(66 citation statements)

References 16 publications

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“…This appears at odds with the data presented herein. However, the authors also report that SW480 colorectal cancer cells with (Myohanen et al, 1998); HCT15 cells are reported to carry a 'high-density of methylation' at p16 INK4a as observed (Zheng et al, 2000). HCT15 cells that express high levels of ascl2 showed evidence for unmethylated DNA only.…”

Section: Discussionmentioning

confidence: 87%

Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

Jubb

Chalasani²,

Frantz³

et al. 2006

Oncogene

121

112

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Achaete-scute like (ASCL)2 is a basic helix-loop-helix transcription factor essential for the maintenance of proliferating trophoblasts during placental development. Using oligonucleotide microarrays we identified ascl2 as a gene significantly upregulated in colorectal adenocarcinomas (n ¼ 36 cancers, n ¼ 16 normals; 15-fold, Po0.0001). This finding was confirmed by quantitative reverse transcriptase (RT)-PCR on large intestinal cancers (n ¼ 29 cancers, n ¼ 16 normals; 10-fold, Po0.0001).In situ hybridization for ascl2 demonstrated expression at the base of small and large intestinal crypts (n ¼ 304), but in no other normal tissues excepting placenta. By in situ hybridization, 52-71% of colorectal adenomas (n ¼ 187), 50-73% of large (n ¼ 327) and 33-64% of small intestinal adenocarcinomas (n ¼ 124) were positive for ascl2 expression. Upregulation of murine ascl2 was also observed using oligonucleotide microarrays, quantitative RT-PCR and in situ hybridization on apc min/ þ and apc 1638N/ þ smad4 À/ þ tumours. Tumour cell lines stably transfected with LEF1 DN or APC2, or transiently transfected with short-interfering RNA (siRNA) against b-catenin showed a significant downregulation of ascl2. Colocalization of ascl2 with nuclear b-catenin was observed in 73 small intestinal adenocarcinomas (P ¼ 0.0008) and apc min/ þ tumours. Preliminary in vitro data suggest ascl2 may promote progression through the G2/M cell cycle checkpoint. In summary, ascl2 is a putative regulator of proliferation that is overexpressed in intestinal neoplasia.

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Section: Discussionmentioning

confidence: 87%

Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

Jubb

Chalasani²,

Frantz³

et al. 2006

Oncogene

121

112

View full text Add to dashboard Cite

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“…Zheng et al (2001) reported previously that the partial methylation pattern was associated with relatively low levels of p14ARF in colorectal cancer cell lines. p14ARF mRNA was expressed at extremely low levels in fully methylated cell lines.…”

Section: Discussionmentioning

confidence: 89%

CDH13 promoter region is specifically methylated in poorly differentiated colorectal cancer

et al. 2004

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It has recently become clear that CDH13 (H-cadherin, T-cadherin) expression is frequently silenced by aberrant methylation in colorectal cancers and adenomas. In this study, we investigated the methylation status of CDH13 gene and detected aberrant promoter methylation in 27 of 84 (32%) colorectal cancers. We then correlated the results with the clinicopathological features of affected patients. We found a significant difference in histology (P ¼ 0.0053) when we compared the CDH13 methylation of poorly differentiated colorectal cancers to that of differentiated ones. This result suggested that poorly differentiated colorectal cancers specifically exhibited CDH13 methylation, and since CDH13 might be responsible for selective cell recognition and adhesion, inactivation of CDH13 could lead to the formation of scattered carcinoma cells in these cancers. There is now good evidence that a series of genetic alterations in both dominant oncogenes and tumour suppressor genes are involved in the pathogenesis of human colorectal cancer. Activation of oncogenes such as the ras gene, and inactivation of tumour suppressor genes such as the APC and p53 genes have been identified in colorectal cancer (Bos et al, 1987;Baker et al, 1990;Nishisho et al, 1991). In addition, we found that several other genes are related to the pathogenesis of colorectal cancer (Hibi et al, 1996;Hibi et al, 1997;Hibi et al, 2002;Yamazaki et al, 2002). An investigation of genetic changes is important to clarify the tumorigenic pathway of colorectal cancer (Vogelstein et al, 1988).Several tumour suppressor genes contain CpG islands in their promoters, prompting many studies that investigate the role of methylation in silencing these genes. Many tumour suppressor genes show evidence of methylation silencing, providing a new potential pathway for the deactivation of tumour suppressor genes (Herman et al, 1996). It has recently become clear that CDH13 (H-cadherin, T-cadherin) expression is frequently silenced by aberrant methylation in colorectal cancers and adenomas (Toyooka et al, 2002). CDH13 encodes a protein belonging to the cadherin family of cell surface glycoproteins responsible for selective cell recognition and adhesion (Takeichi, 1991). Ubiquitous methylation of CDH13 in colorectal cancers and adenomas indicated that such methylation occurs at an early stage in the multistage process of oncogenesis. However, we do not yet know what roles CDH13 methylation play in colorectal cancers.In this study, we investigated the methylation status of CDH13 in 84 colorectal cancers that were examined pathologically. We then correlated the results with the clinicopathological features of affected patients. MATERIALS AND METHODS Sample collection and DNA preparationA total of 84 primary tumours and corresponding colorectal epithelial tissues were collected at the Nagoya University School of Medicine from Japanese colorectal cancer patients who had been diagnosed histologically. These samples were obtained during surgery. All tissues were quickly frozen in liq...

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“…Zheng et al (2000) reported previously that a partial methylation pattern was associated with relatively low levels of p14ARF in colorectal cancer cell lines. p14ARF mRNA was expressed at extremely low levels in fully methylated cell lines, and p14ARF expression in the partial methylated LoVo cell line was intermediate.…”

Section: Discussionmentioning

confidence: 91%

Methylation pattern of CDH13 gene in digestive tract cancers

et al. 2004

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Recently, the loss of CDH13 (T-cadherin, H-cadherin) gene expression accompanied by CDH13 promoter methylation was identified in colon cancers. We examined CDH13 methylation in oesophageal and gastric carcinomas. Five of 37 oesophageal cancers (14%) and 23 of 66 gastric cancers (35%) demonstrated abnormal methylation of the CDH13 promoter. Abnormal methylation was frequently found in gastric cancers of patients at all clinical stages just as in E-cadherin, another of the cadherin family, suggesting that these cancers could be methylated at an early stage. These results suggested that CDH13 might play a variety of roles depending on the tissue type.

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Correlations of partial and extensive methylation at the p14ARF locus with reduced mRNA expression in colorectal cancer cell lines and clinicopathological features in primary tumors

Cited by 79 publications

References 16 publications

Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

Achaete-scute like 2 (ascl2) is a target of Wnt signalling and is upregulated in intestinal neoplasia

CDH13 promoter region is specifically methylated in poorly differentiated colorectal cancer

Methylation pattern of CDH13 gene in digestive tract cancers

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