Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers

Yanagawa, Naoki; Tamura, Gen; Oizumi, Hiroyuki; Kanauchi, Naoki; Endoh, Masao; Sadahiro, Mitsuaki; Motoyama, Teiichi

doi:10.1016/j.lungcan.2007.05.011

Cited by 103 publications

(84 citation statements)

References 37 publications

(39 reference statements)

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“…These data are in agreement with the known tumour suppressor function of members of the Runt family of transcription factors. Thus, Runx2 and Runx3 might act as tumour suppressors in malignant melanoma (Martinez et al, 2005), and Runx3 in breast, gastric, colon, and hepatocellular carcinomas, as well as non-small cell lung cancer (Goel et al, 2004;Sakakura et al, 2005;Lau et al, 2006;Miyagawa et al, 2006;Yanagawa et al, 2007). The reason why the potential tumour suppressor Runx2 is overexpressed in some pancreatic cancer tissues is currently not known, and requires further studies.…”

Section: Discussionmentioning

confidence: 99%

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

et al. 2007

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Recent evidence suggests that Runt-related transcription factors play a role in different human tumours. In the present study, the localisation of the Runt-related transcription factor-2 (Runx2), its transcriptional activity, as well as its regulation of expression was analysed in human pancreatic ductal adenocarcinoma (PDAC). Quantitative real-time PCR and immunohistochemistry were used for Runx2 expression and localisation analysis. Runt-related transcription factor-2 expression was silenced using specific siRNA oligonucleotides in pancreatic cancer cells (Panc-1) and immortalised pancreatic stellate cells (IPSCs). Overexpression of Runx2 was achieved using a full-length expression vector. TGF-b1, BMP2, and other cytokines were assessed for their potential to regulate Runx2 expression. There was a 6.1-fold increase in median Runx2 mRNA levels in PDAC tissues compared to normal pancreatic tissues (Po0.0001). Runt-related transcription factor-2 was localised in pancreatic cancer cells, tubular complexes, and PanIN lesions of PDAC tissues as well as in tumour-associated fibroblasts/stellate cells. Coculture of IPSCs and Panc-1 cells, as well as treatment with TGF-b1 and BMP2, led to increased Runx2 expression in Panc-1 cells. Runt-related transcription factor-2 overexpression was associated with decreased MMP1 release as well as decreased growth and invasion of Panc-1 cells. These effects were reversed by Runx2 silencing. In conclusion, Runx2 is overexpressed in PDAC, where it is regulated by certain cytokines such as TGF-b1 and BMP2 in an auto-and paracrine manner. In addition, Runx2 has the potential to regulate the transcription of extracellular matrix modulators such as SPARC and MMP1, thereby influencing the tumour microenvironment.

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Section: Discussionmentioning

confidence: 99%

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

et al. 2007

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“…To date, the prevalence of RASSF1A methylation is exhibited in 30-40% of NSCLC, and is mainly detected by methylation-specific PCR (MSP) analysis Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Lin et al, 2009;Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011;. However, association of RASSF1A promoter methylation with NSCLC have mostly been investigated in studies with small sample sizes or other limitations in study design, leading to conflicting results, especially in the relationship between RASSF1A promoter methylation and clinicopathologic features among NSCLC.…”

Section: Associations Between Rassf1a Promoter Methylation and Nsclc:mentioning

confidence: 99%

“…Moreover, one was excluded as a duplicate publication . Ultimately, 19 publications met the inclusion criteria (Figure 1) Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Kim et al, 2007;Yanagawa et al, 2007;Yang et al, 2007;Liu et al, 2008;Lin et al, 2009;Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011;Li et al, 2012) and were included in the meta-analysis. Detailed characteristics of the 19 studies are listed in Table 1.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Detailed characteristics of the 19 studies are listed in Table 1. Overall, 5 of the included articles were published in Chinese Peng et al, 2010;Zhang et al, 2010;Kang et al, 2011;Song et al, 2011), and the others were published in English Toyooka et al, 2003;Guo et al, 2004;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Yanagawa et al, 2007;Liu et al, 2008;Li et al, 2012). The aforementioned 19 studies provided data regarding RASSF1A promoter methylation in 2063 cases of NSCLC tissues and 1184 controls of non-tumor tissues, with a total sample size of 3247 cases.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Controls were mainly matched for sex and age. Among the controls, 14 studies were autogenous (tissues from corresponding adjacent normal tissues) Toyooka et al, 2003;Wang et al, 2004;Choi et al, 2005;Dammann et al, 2005;Ito et al, 2005;Chen et al, 2006;Hsu et al, 2007;Kim et al, 2007;Yanagawa et al, 2007;Liu et al, 2008;Song et al, 2011), and 5 were heterogeneous (tissues from non-cancerous respiratory diseases) (Lin et …”

Section: Study Characteristicsmentioning

confidence: 99%

See 2 more Smart Citations

Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data

Liu¹,

Tan²,

Guo³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Background: RASSF1A has been reported to be a candidate tumor suppressor in non-small cell lung cancer (NSCLC). However, the association between RASSF1A promoter methylation and NSCLC remains unclear, particularly in regarding links to clinicopathologic features. Methods: Eligible studies were identified through searching PubMed, EMBASE, Cochrane Library and China National Knowledge Infrastructure (CNKI) databases. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Keywords: RAS associations domain family protein 1A -non-small cell lung cancer -methylation -odds ratio

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Cadherin 13 in cancer

Андреева

Kutuzov

2010

Genes Chromosomes & Cancer

102

109

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We review the evidence suggesting the involvement of Cadherin 13 (CDH13, T-cadherin, H-cadherin) in various cancers. CDH13 is an atypical member of the cadherin family, devoid of a transmembrane domain and anchored to the exterior surface of the plasma membrane via a glycosylphosphatidylinositol anchor. CDH13 is thought to affect cellular behavior largely through its signaling properties. It is often down-regulated in cancerous cells. CDH13 down-regulation has been associated with poorer prognosis in various carcinomas, such as lung, ovarian, cervical and prostate cancer. CDH13 re-expression in most cancer cell lines inhibits cell proliferation and invasiveness, increases susceptibility to apoptosis, and reduces tumor growth in in vivo models. These properties suggest that CDH13 may represent a possible target for therapy in some cancers. At the same time, CDH13 is up-regulated in blood vessels growing through tumors and promotes tumor neovascularization. In contrast to most cancer cell lines, CDH13 overexpression in endothelial cells promotes their proliferation and migration, and has a pro-survival effect. We also discuss molecular mechanisms that may regulate CDH13 expression and underlie its roles in cancer.

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Promoter hypermethylation of RASSF1A and RUNX3 genes as an independent prognostic prediction marker in surgically resected non-small cell lung cancers

Cited by 103 publications

References 37 publications

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

Regulation and functional role of the Runt-related transcription factor-2 in pancreatic cancer

Associations Between RASSF1A Promoter Methylation and NSCLC: A Meta-analysis of Published Data

Cadherin 13 in cancer

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