Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs

Kikuchi, Takefumi; Daigo, Yataro; Katagiri, Toyomasa; Tsunoda, Tatsuhiko; Okada, Koichi; Kakiuchi, Soji; Zembutsu, Hitoshi; Furukawa, Yoichi; Kawamura, Masafumi; Kobayashi, Koichi; Imai, Kohzoh; Nakamura, Yusuke

doi:10.1038/sj.onc.1206288

Cited by 296 publications

(255 citation statements)

References 25 publications

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“…After amplified RNAs (aRNAs) were labeled with Cy3 or Cy5, respectively, we carried out hybridization between labeled aRNAs and cDNA microarray slides containing 36 864 spots and detected the signals. Expression of CDC20 in various cancer tissues and their corresponding normal tissues were examined by using data sets that were analysed previously (Ono et al, 2000;Kitahara et al, 2001;Okabe et al, 2001;Hasegawa et al, 2002;Kaneta et al, 2002;Kitahara et al, 2002;Nagayama et al, 2002;Okutsu et al, 2002;Kikuchi et al, 2003;Okada et al, 2003;Ashida et al, 2004;Jinawath et al, 2004;Nakamura et al, 2004;Nishidate et al, 2004;Ochi et al, 2004;Obama et al, 2005;Takata et al, 2005;Hirota et al, 2006;Taniwaki et al, 2006;Yamabuki et al, 2006). To select genes that were suppressed by p53 and upregulated in various cancer tissues, the following two criteria were used: (1) genes whose expression were more than threefold decreased by Ad-p53 and (2) genes whose expression were more than threefold increased in various cancer tissues compared with its corresponding normal tissues.…”

Section: Cdna Microarraysmentioning

confidence: 99%

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

et al. 2007

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The p53 protein inhibits malignant transformation through direct and indirect regulation of transcription of many genes related to cell cycle, apoptosis and cellular senescence. A number of genes induced by p53 have been well characterized, but biological significance of genes whose expression was suppressed by p53 is still largely undisclosed. To clarify the roles of p53-suppressive genes in carcinogenesis, we analysed two data sets of wholegenome expression profiles, one for cells in which wildtype p53 was exogenously introduced and the other for a large number of clinical cancer tissues. Here, we identified CDC20 that was frequently upregulated in many types of malignancies and remarkably suppressed by ectopic introduction of p53. CDC20 expression was suppressed by genotoxic stresses in p53-and p21-dependent manners through CDE-CHR elements in the CDC20 promoter. Furthermore, small interference RNA (siRNA)-mediated silencing of p53 induced CDC20 expression in normal human dermal fibroblast cells. As we expected, treatment of cancer cells with siRNA against CDC20 induced G 2 /M arrest and suppressed cell growth. Our results indicate that p53 inhibits tumor cell growth through the indirect regulation of CDC20 and that CDC20 might be a good potential therapeutic target for a broad spectrum of human cancer.

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Section: Cdna Microarraysmentioning

confidence: 99%

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

et al. 2007

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“…Kikuchi and colleagues have performed several innovative studies trying to correlate a patient's gene expression profile to select the best chemotherapy regimen for that individual [43]. They performed cDNA microarray analysis of 37 NSCLCs after laser-capture microdissection of cancer cells from primary tumors.…”

Section: To Optimize Therapy For a Given Patientmentioning

confidence: 99%

Gene expression profiling of Non-small cell lung cancer

et al. 2008

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Functional genomics has emerged over the past ten years as a novel technology to study genetic alterations. Gene expression arrays are one genomic technique employed to discover changes in the DNA expression that occur in neoplastic transformation. Microarrays have been applied to investigating lung cancer. Specific applications include discovering novel genetic changes that occur in lung tumors. Microarrays can also be applied to improve diagnosis, staging, and discover prognostic markers. The eventual goal of this technology is to discover new markers for therapy and to customize therapy based on an individual tumor genetic composition. In this review, we present the current state of gene expression array technology in its application to lung cancer.

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“…As a result, it causes masked chain termination (9,10). GEM sensitivity of cells is known to be affected by pathways that involve ribonucleotide reductase E2F1 and Bcl-2 (11)(12)(13). However, these pathways cannot account for all of the biological effects of GEM on cells, and therefore other pathways should be investigated.…”

Section: Introductionmentioning

confidence: 99%

Molecular features linked to the growth-inhibitory effects of gemcitabine on human pancreatic cancer cells

Toshimitsu

Iizuka²,

Yamamoto³

et al. 2006

Oncol Rep

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Abstract. Although gemcitabine (GEM) is widely used in the treatment of pancreatic cancers, the molecular mechanisms that underlie its anti-tumor effects are not fully understood. To clarify the anti-tumor mechanism(s) of GEM, we studied a human pancreatic cancer cell line, YPK-1, that showed a 50% inhibitory concentration (IC50) of GEM of 6.3x10 -3 μg/ml after 72 h of exposure. Cell proliferation was perturbed by 6 to 72 h of exposure to GEM concentrations equal to one-half or one-quarter of the IC50. We used cDNA microarrays containing 2976 genes to identify genes with expression affected by exposure to GEM. The self-organizing map identified nine clusters, including 85 and 87 genes, that showed differential expression in response to exposure to one half and one quarter IC50 GEM, respectively. Of these, 24 genes were common to cells exposed to the two different concentrations of GEM. Most are signal transduction or transcription-related genes. The microarray data for two of these genes, SPARC and RPS8, were validated by RT-PCR. Although further studies are needed to examine whether the changes in expression profiles of these genes are specific to cells exposed to GEM, the present data provide insights into the anti-tumor effects of GEM on pancreatic cancers.

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Expression profiles of non-small cell lung cancers on cDNA microarrays: Identification of genes for prediction of lymph-node metastasis and sensitivity to anti-cancer drugs

Cited by 296 publications

References 25 publications

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

CDC20, a potential cancer therapeutic target, is negatively regulated by p53

Gene expression profiling of Non-small cell lung cancer

Molecular features linked to the growth-inhibitory effects of gemcitabine on human pancreatic cancer cells

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