Identification of differentially expressed genes in nasopharyngeal carcinoma by means of the Atlas human cancer cDNA expression array.
ABSTRACT To investigate genes of critical areas, including cell cycle/growth control, apoptosis, oncogene/tumor suppressors and growth factor/cytokines, that are differentially expressed in nasopharyngeal carcinoma.
The Human Cancer cDNA Atlas, which contains 588 genes relating to tumor biology, was used to screen normal nasopharyngeal tissue, nasopharyngeal cancer (NPC). The reverse transcription/polymerase chain reaction was used to confirm the expression pattern of some genes identified by Atlas hybridization.
The differentially expressed cell cycle/growth control regulators in NPC showed a stronger tendency toward cell proliferation with the up-regulation of cyclin D1, cyclin D2 etc. The expression pattern of apoptosis-related genes demonstrated the up-regulation of both anti-apoptotic factors such as the BCL-2-related protein A1, TRAF3, the inhibitor of apoptosis protein A1 (IAPI) and apoptotic pathway elements such as Fas/Apo-1, Apo-2 ligand etc. Among oncogenes/tumor suppressors, MDM2, STAT1 and STAT2 were found to be up-regulated in NPC. The expression profile of growth factors/cytokines showed the up-regulation of many growth-enhancing factors such as EGR1, tumor-derived growth factor 1, platelet-derived growth factor A chain etc. as well as Th1-type cytokines e.g. interleukin-1beta and interferons. A smaller number of genes were down-regulated in nasopharyngeal cancer, such as those encoding ERK1, Raf, secreted apoptosis-related protein 1, CD27BP, transforming growth factor beta2, pre-B-cell-stimulating factor homologue etc.
The consistent tendency toward cell proliferation, the possibility of a stronger antiapoptotic force that operates on the normal apoptotic pathway, or the autocrine or paracrine growth factors may account for the development of NPC. Some genes are reported for the first time to have changed expression in nasopharyngeal carcinoma. The simple, quick, and high-throughput method of profiling gene expression by cDNA array hybridization provides us with a quick overview of key factors that may be involved in NPC, and may identify genes suitable for further study of carcinogenesis mechanism or targets for possible molecular diagnosis or therapy.
- SourceAvailable from: Yue Cheng
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- "BCAT1 (branched chain amino acid transaminase 1, cytosolic) Induces cell proliferation, migration, and invasion  BCL2 (B-cell CLL/lymphoma 2) Inhibits apoptosis    CCND1 (cyclin D1) Promotes cell cycle G 1 -S transition through regulation of pRb    DeltaNp63/TP73L [tumor protein p73-like, p63 splicing variants lacking NH(2)-terminal transactivating domain] "
ABSTRACT: The interplay between host cell genetics and Epstein-Barr virus (EBV) infection contributes to the development of nasopharyngeal carcinoma (NPC). Understanding the host genetic and epigenetic alterations and the influence of EBV on cell signaling and host gene regulation will aid in understanding the molecular pathogenesis of NPC and provide useful biomarkers and targets for diagnosis and therapy. In this review, we provide an update of the oncogenes and tumor suppressor genes associated with NPC, as well as genes associated with NPC risk including those involved in carcinogen detoxification and DNA repair. We also describe the importance of host genetics that govern the human leukocyte antigen (HLA) complex and immune responses, and we describe the impact of EBV infection on host cell signaling changes and epigenetic regulation of gene expression. High-power genomic sequencing approaches are needed to elucidate the genetic basis for inherited susceptibility to NPC and to identify the genes and pathways driving its molecular pathogenesis.Ai zheng = Aizheng = Chinese journal of cancer 11/2014; 33(11):556-68. DOI:10.5732/cjc.014.10170
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- "MYC (Baba et al., 2001) ϩ3q13.1–26.2 TNFSF10 (Xie et al., 2000) ϩ1q22–32 LAMC2 (Hui et al., 2002), ABL2 (Li et al., 2001a) "
ABSTRACT: Pathogenesis of nasopharyngeal carcinoma (NPC) is a multistep and multipathway process that cannot be fully explained by a fixed linear progression model. We used distance-based and branching-tree methods to construct more general tree-like models for NPC carcinogenesis from 170 comparative genomic hybridization (CGH) samples previously published in five smaller studies. Imbalances were classified into "overlap regions," each containing the most commonly gained or lost band on each chromosome arm as well as adjacent bands that were gained or lost almost as often. The chromosome abnormalities associated with NPC were -3p26-13 (48.9%), -11q22-25 (38.1%), -16q12-24 (38.1%), -14q24-32 (32.4%), -13q21-32 (22.3%), -9p23-21(21.6%), +12p12 (46%), +12q13-15 (43.9%), +1q22-32 (33.1%), +3q13.1-26.2 (30.2%), and +8q22.1-24.2 (27.3%). NPC can be classified into two groups, one marked by +12p12 and +8q22.1-24.2 and the other by -3p26-13, -11q22-25, -14q24-32, and +1q22-32. The tree models predicted -3p26-13 and +12p12 as early events and +8q22.1-24.2 as a late event. The predictions for -3p26-13 and +8q22.1-24.2 were consistent with previous studies. The prediction for +12p12 is being reported for the first time. Many known NPC-related genes on chromosomal regions of these tree models are discussed, some of which may merit additional study. The potential applications of tree models are also discussed.Genes Chromosomes and Cancer 09/2004; 40(4):307-15. DOI:10.1002/gcc.20036 · 3.84 Impact Factor
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- "The sequences reported here had a consistent DD profile across the tumour samples, whereas other bands (about 20%) with tumour stage-specific profiles need to be studied further with a larger number of tumours. Only eight out of 70 genes overlap between our and other profiles of HNSCC (Leethanakul et al, 2000; Alevizos et al, 2001; Al Moustafa et al, 2002; Belbin et al, 2002; El-Naggar et al, 2002; Mendez et al, 2002; Xie et al, 2000), possibly because, in contrast to these other studies, we did not restrict the profiling to particular genes on arrays, since PCR-DD samples the whole transcriptome. Moreover, we restricted our analysis to a very specific site. "
ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in men with an incidence of about 780000 new cases per year worldwide and a poor rate of survival. There is a need for a better understanding of HNSCC, for the development of rational targeted interventions and to define new prognostic or diagnostic markers. To address these needs, we performed a large-scale differential display comparison of hypopharyngeal HNSCCs against histologically normal tissue from the same patients. We have identified 70 genes that exhibit a striking difference in expression between tumours and normal tissues. There is only a limited overlap with other HNSCC gene expression studies that have used other techniques and more heterogeneous tumour samples. Our results provide new insights into the understanding of HNSCC. At the genome level, a series of differentially expressed genes cluster at 12p12-13 and 1q21, two hotspots of genome disruption. The known genes share functional relationships in keratinocyte differentiation, angiogenesis, immunology, detoxification, and cell surface receptors. Of particular interest are the 13 'unknown' genes that exist only in EST, theoretical cDNA and protein databases, or as chromosomal locations. The differentially expressed genes that we have identified are potential new markers and therapeutic targets.British Journal of Cancer 12/2003; 89(10):1940-9. DOI:10.1038/sj.bjc.6601373 · 4.82 Impact Factor