Proteomic identification of differentially‐expressed genes in human gastric carcinomas

Nishigaki, Ryuichi; Osaki, Mitsuhiko; Hiratsuka, Masanori; Toda, Tosifusa; Murakami, Kaori; Jeang, Kuan‐Teh; Ito, Hisao; Inoue, Toshiaki; Oshimura, Mitsuo

doi:10.1002/pmic.200401307

Cited by 104 publications

(80 citation statements)

References 43 publications

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“…All of the carcinoma specimens were histologically diagnosed as advanced carcinoma. They found CYR61 protein was down-regulated in gastric carcinoma tissues as compared with normal gastric mucosae (45). The discrepancy between that study and the current one might be due to different study design.…”

Section: Discussioncontrasting

confidence: 45%

“…It has recently been reported that CYR61 is down-regulated in a proteomics analysis study in human gastric carcinomas using two-dimensional gel studies, independent of antibody (45). In that study, the authors used a proteomic approach to search for genes that may be involved in gastric carcinogenesis and that might serve as diagnostic markers.…”

Section: Discussionmentioning

confidence: 99%

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Elevated Expression of Cyr61 Enhances Peritoneal Dissemination of Gastric Cancer Cells through Integrin α2β1

Lin∥

Chang

Lin

et al. 2007

Journal of Biological Chemistry

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Cysteine-rich 61 (Cyr61/CCN1) is involved in human gastric cancer development and progression. Nonetheless, the role of Cyr61 as regards peritoneal dissemination of such cancers has not yet been completely characterized. We used liposome-mediated transfection to establish Cyr61, or antisense Cyr61, expression vectors into gastric cancer AGS or MKN45 cell lines. Transfectants were tested by means of a cancer-cell adhesion assay in vitro and ex vivo. Furthermore, a functional integrin fluorescence-activated cell sorting assay, reverse transcription-PCR, and an AP-1 reporter assay were performed to investigate the potential signaling pathway of Cyr61. It was shown that stable transfection of Cyr61 into the AGS cell line strongly enhanced its adhesion ability. The overexpression of Cyr61 within AGS cells significantly increased the functional expression of integrin ␣ 2 ␤ 1 . Function-neutralizing antibody to integrin ␣ 2 ␤ 1 effectively suppressed the Cyr61-mediated enhanced adhesion of AGS cells to peritoneal tissue. Promoter assays of integrin ␣2 gene further revealed that the AP-1 pathway was evidently activated within Cyr61-expressing AGS cells. Animal studies have revealed that mice injected with Cyr61-overexpressed AGS cells featured a greater number of peritoneal seeding nodules and a lower survival rate than the Neo control cell lines, and when such cells were treated with functional blocking antibody to integrin ␣ 2 ␤ 1 , they were able to elicit a decline in the peritoneal dissemination. The data suggest that Cyr61 may contribute to the peritoneal dissemination of gastric cancer by promoting tumor-cell adhesion ability through the up-regulation of the functional integrin ␣ 2 ␤ 1 via an AP-1-dependent pathway.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Elevated Expression of Cyr61 Enhances Peritoneal Dissemination of Gastric Cancer Cells through Integrin α2β1

Lin∥

Chang

Lin

et al. 2007

Journal of Biological Chemistry

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“…Although this point remains unclear, our study underscores a possible link between the acetylation status of tubulin and entry to chromosome condensation. In this context, it is notable that our previous proteomic studies found that the expression of a group of tubulin-related proteins is altered in gliomas or gastric carcinomas in comparison to normal tissues (Hiratsuka et al, 2003;Nishigaki et al, 2005). Although SIRT2 as a novel mitotic checkpoint protein T Inoue et al how CHFR contributes to mitotic checkpoints is not fully understood, several mechanisms of CHFR function have been proposed.…”

Section: Discussionmentioning

confidence: 99%

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress

et al. 2006

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We previously identified SIRT2, an nicotinamide adenine dinucleotide (NAD)-dependent tubulin deacetylase, as a protein downregulated in gliomas and glioma cell lines, which are characterized by aneuploidy. Other studies reported SIRT2 to be involved in mitotic progression in the normal cell cycle. We herein investigated whether SIRT2 functions in the mitotic checkpoint in response to mitotic stress caused by microtubule poisons. By monitoring chromosome condensation, the exogenously expressed SIRT2 was found to block the entry to chromosome condensation and subsequent hyperploid cell formation in glioma cell lines with a persistence of the cyclin B/cdc2 activity in response to mitotic stress. SIRT2 is thus a novel mitotic checkpoint protein that functions in the early metaphase to prevent chromosomal instability (CIN), characteristics previously reported for the CHFR protein.We further found that histone deacetylation, but not the aberrant DNA methylation of SIRT2 5 0 untranslated region is involved in the downregulation of SIRT2. Although SIRT2 is normally exclusively located in the cytoplasm, the rapid accumulation of SIRT2 in the nucleus was observed after treatment with a nuclear export inhibitor, leptomycin B and ionizing radiation in normal human fibroblasts, suggesting that nucleo-cytoplasmic shuttling regulates the SIRT2 function. Collectively, our results suggest that the further study of SIRT2 may thus provide new insights into the relationships among CIN, epigenetic regulation and tumorigenesis. Oncogene (2007) 26, 945-957.

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“…In addition, all spots with differing intensity between normal and GC tissue were rechecked in 8 pairs of 2-DE images from each sample pair, to identify those with a high incidence rate. A significant difference in the expression of a protein between tumor and normal tissue was defined as >2-fold change in spot density in >30% of tumor specimens (9).…”

Section: Protein Separation By Two-dimensional Gel Electrophoresis (2mentioning

confidence: 99%

Proteomics-based identification of a group of apoptosis-related proteins and biomarkers in gastric cancer

Bai

Ye²,

Liang³

et al. 2011

Int J Oncol

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Abstract. Gastric cancer (GC) is the one of the most common types of cancer in Asia. To better understand the molecular mechanisms underlying GC, and to seek new markers of tumor progression, we used a proteomics strategy to analyze the protein expression patterns in matched pairs of GC tissue and normal gastric mucosa of 8 GC patients. Comparative proteomic analysis, using two-dimensional gel electrophoresis (2-DE) and matrix-assisted laser-desorption ionization timeof-flight mass spectrometry (MALDI-TOF-MS), revealed that 32 protein spots showed a >2-fold difference in intensity between tumor and normal tissues. Twenty-six proteins were up-regulated and 6 proteins were down-regulated in tumor tissue compared to control. Western blot analysis confirmed differential expression for 9 proteins, including AGR2, ENO1, GDI2, GRP78, GRP94, PPIA, PRDX1, PTEN and VDAC1. Immunohistochemical staining of a tissue microarray, derived from 145 GC patients, with antibodies for each of the 9 proteins demonstrated a significant association between the level of protein immunostaining and the clinical features of the disease in the donor. The identified proteins were functionally classified using bioinformatics methods, showing that the 9 proteins identified were related to BCL2, BAX, ERBB2 and CASP3 proteins and involved in the process of apoptosis. These proteomic data provide potentially valuable insights into both the biology of GC and the identity of biomarkers for tumor progression. We propose ENO1, GRP78, GRP94, PPIA, PRDX1 and PTEN as potential GC biomarkers.

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Proteomic identification of differentially‐expressed genes in human gastric carcinomas

Cited by 104 publications

References 43 publications

Elevated Expression of Cyr61 Enhances Peritoneal Dissemination of Gastric Cancer Cells through Integrin α2β1

Elevated Expression of Cyr61 Enhances Peritoneal Dissemination of Gastric Cancer Cells through Integrin α2β1

SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress

Proteomics-based identification of a group of apoptosis-related proteins and biomarkers in gastric cancer

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