Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

Saigusa, Susumu; Tanaka, Koji; Toiyama, Yuji; Matsushita, Kohei; Kawamura, Mikio; Okugawa, Yoshinaga; Hiro, Junichiro; Inoue, Yasuhiro; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

doi:10.3892/or.2012.1863

Cited by 24 publications

(23 citation statements)

References 38 publications

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“…Reasons for this lack of effect may rely in aspects favoring a tighter MATα2 2 -MATβ interaction or additional interactions [10, 18], which could preclude MATα2-PDRG1 interaction and the effects on DNA methylation. Additionally, aberrant DNA methylation is a well-established characteristic of cancer cells [57], and recent studies demonstrated global DNA hypomethylation correlating with enhanced expression of PDRG1 in a variety of human non-hepatic tumors [56, 58, 59]. In our study, no morphological changes or apoptosis are detected upon PDRG1 overexpression, confirming previous reports [43].…”

Section: Discussionsupporting

confidence: 91%

The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases

et al. 2016

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Methionine adenosyltransferases MAT I and MAT III (encoded by Mat1a) catalyze S-adenosylmethionine synthesis in normal liver. Major hepatic diseases concur with reduced levels of this essential methyl donor, which are primarily due to an expression switch from Mat1a towards Mat2a. Additional changes in the association state and even in subcellular localization of these isoenzymes are also detected. All these alterations result in a reduced content of the moderate (MAT I) and high Vmax (MAT III) isoenzymes, whereas the low Vmax (MAT II) isoenzyme increases and nuclear accumulation of MAT I is observed. These changes derive in a reduced availability of cytoplasmic S-adenosylmethionine, together with an effort to meet its needs in the nucleus of damaged cells, rendering enhanced levels of certain epigenetic modifications. In this context, the putative role of protein-protein interactions in the control of S-adenosylmethionine synthesis has been scarcely studied. Using yeast two hybrid and a rat liver library we identified PDRG1 as an interaction target for MATα1 (catalytic subunit of MAT I and MAT III), further confirmation being obtained by immunoprecipitation and pull-down assays. Nuclear MATα interacts physically and functionally with the PDRG1 oncogene, resulting in reduced DNA methylation levels. Increased Pdrg1 expression is detected in acute liver injury and hepatoma cells, together with decreased Mat1a expression and nuclear accumulation of MATα1. Silencing of Pdrg1 expression in hepatoma cells alters their steady-state expression profile on microarrays, downregulating genes associated with tumor progression according to GO pathway analysis. Altogether, the results unveil the role of PDRG1 in the control of the nuclear methylation status through methionine adenosyltransferase binding and its putative collaboration in the progression of hepatic diseases.

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Section: Discussionsupporting

confidence: 91%

The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases

et al. 2016

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“…Following preoperative CRT, TRG scores may reflect the characteristics of proliferation and resistance to hypoxia of residual cancer cells [35] [37]. TRG was reported to have prognostic value in LARC patients after preoperative CRT, and has also been previously reported as an independent prognostic factor for local recurrence [5,38,39].…”

Section: Discussionmentioning

confidence: 98%

Relationships Between SMAD3 Expression and Preoperative Fluoropyrimidine‐Based Chemoradiotherapy Response in Locally Advanced Rectal Cancer Patients

et al. 2015

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“…Until now, the mechanism of tumor recurrence in colon cancer after cutative therapy has not been fully elucidated. But there is a widely accepted explanation for tumor reinitiation that the remnant of colon cancer stem cell has responsibility for relaps of tumors which have been removed or chemically compromised [22][23][24]. Therefore, colon cancer stem cells (CSCs) are the optimum targets for cure although the cellular origin of CSCs has not been clearly determined yet.…”

Section: Discussionmentioning

confidence: 99%

Over-expression of LGR5 correlates with poor survival of colon cancer in mice as well as in patients

Liu¹,

Dai²,

Lian³

et al. 2014

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Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) was identified as the stem cell marker of colon cancer stem cells (CSCs), which were considered as the main criminal cells initiation and reinitiation of colon cancer. We intended to demonstrate and further explain the relationship between LGR5 and colon cancer in mice model and patients. In our research, we used transcriptional methods and immunohistochemistry to investigate the LGR5 gene and protein expression, examined proliferating cell nuclear antigen (PCNA) and Ki67 which were the classic markers for cell proliferation in LGR5 protein positive and negative colon cancer among mice model and patients. Our results showed that LGR5 mRNA and protein expression was significantly over-expressed in 193/366 patients and 24/40mice model with primary colon cancer contrasted with matched normal tissues; significantly higher LGR5 gene expression was detected in pT4 cases than that in pT3 cases; PCNA and Ki67 expression was much more increase in colon cancer cells with positive LGR5 expression than those with negative LGR5 expression;LGR5 positive cancer not only in mice model but also in patients have shorter survival rate compared with LGR5 negative cancer. All our study manifested that LGR5 took on an important effect in the initiation and progression of colon cancer, provided also more helpful evidence for clinical diagnosis and an useful indicator for adjuvant therapy.

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Gene expression profiles of tumor regression grade in locally advanced rectal cancer after neoadjuvant chemoradiotherapy

Cited by 24 publications

References 38 publications

The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases

The Oncogene PDRG1 Is an Interaction Target of Methionine Adenosyltransferases

Relationships Between SMAD3 Expression and Preoperative Fluoropyrimidine‐Based Chemoradiotherapy Response in Locally Advanced Rectal Cancer Patients

Over-expression of LGR5 correlates with poor survival of colon cancer in mice as well as in patients

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