Reduced expression of the <i>insulin‐induced protein 1</i> and <i>p41 Arp2/3 complex</i> genes in human gastric cancers

Kaneda, Atsushi; Kaminishi, Michio; Nakanishi, Yukihiro; Sügimura, Takashi; Ushijima, Toshikazu

doi:10.1002/ijc.10464

Cited by 41 publications

(36 citation statements)

References 26 publications

(23 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, other researchers have reported that expression of TGFb2, which is downregulated by HMGA1a overexpression (Table 1), is correlated with phenotypically less malignant human breast cancers that respond better to tamoxifen chemotherapy (Kopp et al, 1995;Brandt et al, 2003). Likewise, it has been shown that expression of the insulin-induced protein 1 gene is significantly decreased in human gastric cancers (Kaneda et al, 2002), and here we demonstrate that the expression of this gene is downregulated approximately 2.5-fold in cells overexpressing the HMGA1a protein (Table 1). Recently, Charpentier et al (2000) reported that the expression of the estradiol-induced hypothetical protein, E2IG4, is increased in MCF-7 cells following exposure to mitogenic concentrations of estrogen (Charpentier et al, 2000).…”

Section: Discussionsupporting

confidence: 82%

High-mobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells

et al. 2004

View full text Add to dashboard Cite

High-mobility group (HMG) A1 proteins are gene regulatory factors whose overexpression is frequently observed in naturally occurring human cancers. The overexpression of transgenic HMGA1 proteins in cells results in neoplastic transformation and promotes progression to malignant cellular phenotypes. To understand the underlying molecular and biological events involved in these phenomena, we used oligonucleotide microarray analyses to generate an HMGA1a-induced expression profile for approximately 22 000 genes. This gene expression profile was generated using a well-characterized transgenic human MCF-7 mammary adenocarcinoma cell line in which overexpression of transgenic HMGA1 promotes a transition to a more malignant and metastatic phenotype. Microarray expression analyses, together with independent quantitative real-time reverse transcriptase polymerase chain reaction results, indicate that HMGA1a regulates genes involved in the Ras-extracellular signalrelated kinase (Ras/ERK) mitogenic signaling pathway, including KIT ligand and caveolins 1 and 2. We also found that many cholesterol biosynthesis genes were decreased in cells overexpressing HMGA1a. Cholesterol depletion, decreased caveolin, and increased KIT ligand expression, are all independently associated with the activation of Ras/ERK signaling. Upon further analysis, we found that sensitivity to epidermal growth factor activation of ERK phosphorylation was significantly higher, and that cholesterol was significantly depleted, in cells overexpressing HMGA1a. The cumulative evidence indicates that one likely mechanism by which the HMGA1a protein promotes malignant changes in cells is through increased sensitivity to the activation of the Ras/ERK signaling pathway.

show abstract

Section: Discussionsupporting

confidence: 82%

High-mobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Kaneda et al, in press). However, DNA fragments from CGIs outside promoter regions can also be isolated by MS-RDA, and some of them are associated with altered gene expression (Kaneda et al, 2002;Takai et al, 2001). Once the role of 3-OST-2 silencing in cancer development and progression is clarified, the presence of its product in the extracellular matrix could be useful as a target for cancer therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Methylation-associated silencing of heparan sulfate D-glucosaminyl 3-O-sulfotransferase-2 (3-OST-2) in human breast, colon, lung and pancreatic cancers

et al. 2003

Self Cite

View full text Add to dashboard Cite

Aberrant CpG methylations play important roles in cancer development and progression. In this study, aberrant methylations in human breast cancer were searched for using methylation-sensitive representational difference analysis (MS-RDA). A CpG island (CGI) in the 5 0 region of the heparan sulfate d-glucosaminyl 3-Osulfotransferase-2 (3-OST-2) gene was found to be hypermethylated, while its exon 2 was hypomethylated. In seven breast cancer cell lines, hypermethylation of the 5 0 region and loss of 3-OST-2 expression were observed. Treatment with a demethylating agent, 5-aza-2 0 -deoxycytidine, removed the methylation of the CGI in the 5 0 region and restored its expression, demonstrating silencing of the 3-OST-2 gene. Methylation-specific PCR (MSP) analysis in 85 primary breast cancers showed that the hypermethylation of the CGI in the 5 0 region was present in 75 (88%) of them. Quantitative reverse transcriptase-PCR (RT-PCR) analysis in 37 primary breast cancers showed that the average expression level was decreased in them. Further, MSP analysis in primary colon, lung and pancreatic cancers showed that hypermethylation of the CGI in the 5 0 region was present in the colon (8/10, 80%), lung (7/10, 70%) and pancreatic (10/10, 100%) cancers. These results showed that silencing of 3-OST-2 was present in a wide range of human cancers. The 3-OST-2 gene encodes an enzyme involved in the final modification step of heparan sulfate proteoglycans (HSPGs), and its silencing is expected to result in abnormal modification of HSPGs and abnormal signal transduction. From the high incidence, silencing of the 3-OST-2 gene is expected to have high diagnostic, and potentially therapeutic, values.

show abstract

“…15 It is known that, even if a peripheral region of a CGI is methylated, its core region is not necessarily methylated. [16][17][18][19] Methylation statuses of the core regions of the 5 0 CGI of the 31 genes were analyzed by MSP in 8 breast cancer cell lines, including MDA-MB-468. All the CGI were unmethylated in HMEC.…”

Section: Isolation Of Cgi Aberrantly Methylated In Human Breast Cancersmentioning

confidence: 99%

Identification of 20 genes aberrantly methylated in human breast cancers

Miyamoto

Fukutomi

Akashi‐Tanaka

et al. 2005

Intl Journal of Cancer

Self Cite

140

101

View full text Add to dashboard Cite

Aberrant methylation of CpG islands (CGI) not only plays a role in gene silencing, but is also a potential cancer biomarker. To identify more CGI aberrantly methylated in human breast cancers, we carried out a genome-wide search for aberrant methylation, using methylation-sensitive-representational difference analysis. CGI in 5 0 upstream regions of 20 genes, TSPAN-2, AK5, LOC284999, HOXD11, FLJ25161, XT3, PCDH10, PCDHGB6, SIM1, LOC346978, COE2, TDH (FLJ25033), LOC346419, FLJ33790, GJB2, AMN, LOC201164, DLX4, DCC and FOXA2, were found to be methylated in at least one of 8 breast cancer cell lines. Fifteen of the 20 genes were methylated in more than one of 21 primary breast cancers in Stages I or II, and especially, those of LOC346978, HOXD11, SIM1, PCDHGB6 and FLJ25161 were methylated in more than 10 cancers. All the breast cancers had some aberrant methylation. Key words: MS-RDA; breast cancer; CpG island; methylation Aberrant methylation of CpG islands (CGI) in promoter regions is known to be involved in silencing of tumor-suppressor genes. 1,2Because the aberrant methylation of tumor-suppressor genes is specific to cancer cells, its detection in biopsy specimens and free DNA in the blood is drawing attention as a tumor marker.3 Aberrantly methylated DNA molecules embedded in the vast majority of normal, unmethylated DNA molecules can be sensitively detected by various techniques, such as methylation-specific PCR (MSP) and quantitative MSP.4,5 Detection of aberrant methylation is more advantageous than detection of mutation in terms of sensitivity. One of the current limitations to the use of aberrant methylation as a tumor marker is the lack of target CGI specifically methylated in cancer cells.Uncovering novel aberrantly methylated CGI is important not only for discovery of novel tumor-suppressor genes, but also for identification of tumor markers. To make a genome-wide screening for novel aberrant methylation, restriction landmark genomic scanning (RLGS), methylation-sensitive-representational difference analysis (MS-RDA) and cDNA microarrays combined with treatment with a demethylating agent have been used.6-8 Most studies, including our previous analysis of human breast cancers, 9,10 have attempted to identify genes silenced in cancers. These studies have paid little attention to the other CGI that are potentially useful as tumor biomarkers even if not related with gene silencing.In our study, to search for aberrantly methylated 5 0 CGI as candidate tumor markers, we analyzed a human breast cancer cell line, MDA-MB-468, by MS-RDA with recent modifications for efficient isolation of CGI. 11,12Material and methods Cell lines, tumor samples, and DNA/RNA extraction MCF-7, ZR-75-1, BT474, T-47D, MDA-MB-231, MDA-MB-468 and SK-BR-3 were purchased from the American Type Culture Collection (Rockville, MD), and YMB-1-E was obtained from the Japanese Collection of Research Bioresources (Tokyo, Japan). Human mammary epithelial cells (HMEC) were purchased from Cambrex (East Rutherford, NJ). Breast cancers (1 carcinom...

show abstract

Reduced expression of the insulin‐induced protein 1 and p41 Arp2/3 complex genes in human gastric cancers

Cited by 41 publications

References 26 publications

High-mobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells

High-mobility group A1a protein regulates Ras/ERK signaling in MCF-7 human breast cancer cells

Methylation-associated silencing of heparan sulfate D-glucosaminyl 3-O-sulfotransferase-2 (3-OST-2) in human breast, colon, lung and pancreatic cancers

Identification of 20 genes aberrantly methylated in human breast cancers

Contact Info

Product

Resources

About