Differential SPARC mRNA expression in Barrett's oesophagus

Brabender, Jan; Lord, Reginald V.; Metzger, Ralf; Park, J; Salonga, Dennis; Danenberg, Kathleen D.; Danenberg, Peter V.; Hölscher, Arnulf H.; Schneider, Paul M.

doi:10.1038/sj.bjc.6601324

Cited by 36 publications

(36 citation statements)

References 22 publications

(28 reference statements)

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“…Interestingly, EGFR overexpression by itself is not prognostic of survival in NSCLC (Rusch et al, 1993;Fontanini et al, 1998;Hirsch et al, 2003). The correlation between EGFR expression and poor survival, however, is more prominent when analysed along with the expression of its dimerization partner, ErbB2, or with its ligands, transforming growth factor-a (TGF-a) and EGF (Brabender et al, 2001;Herbst and Bunn, 2003).…”

Section: Introductionmentioning

confidence: 99%

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants

Yn²,

et al. 2005

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Mutations in the kinase domain of epidermal growth factor receptor (EGFR) are associated with clinical responsiveness to gefitinib in patients with non-small-cell lung cancers (NSCLC). Recently, we have identified many novel EGFR mutations in NSCLC tissues. In this study, we found that gefitinib could suppress the tyrosine phosphorylation of most EGFR mutants better than the wild-type receptor. However, gefitinib had quite variable growth-suppressive effects on different EGFR mutantexpressing cells. All tested EGFR mutants have high basal phosphorylation at multiple tyrosine residues. Upon EGF stimulation, the mutated EGFRs did not have apparently stronger phosphorylation at tyrosines 845, 992, 1068, and 1173 than the wild-type receptor. However, stronger phosphorylation at tyrosine 1045 was observed in the S768I, L861Q, E709G, and G719S mutants. The E746-A750 deletion mutant was less responsive to EGF than the wild-type and other mutant receptors. The S768I, L861Q, E709G, and G719S mutants were refractory to EGFinduced ubiquitination and had more sustained tyrosine phosphorylation. E709G and G719S also lacked EGFinduced receptor downregulation. Our results indicate that, in addition to sensitivity to gefitinib, EGFR mutations also caused various changes in EGFR's regulatory mechanisms, which may contribute to the constitutive activation of EGFR mutants and oncogenesis in NSCLC.

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Section: Introductionmentioning

confidence: 99%

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants

Yn²,

et al. 2005

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“…In fact, it is a poor prognostic factor (Hayashi et al, 2002;Kohya et al, 2002;Brabender et al, 2003), probably due to the finding that patients with epigenetic silencing of MGMT accumulate more mutations (p53 and K-ras). This is an example of the difference between predictive and prognostic markers.…”

Section: Methylation-mediated Silencing Of Mgmt Marks Tumors Sensitivmentioning

confidence: 99%

Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer

2004

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O 6 -methylguanine DNA methyltransferase (MGMT) is a key enzyme in the DNA repair network. MGMT removes mutagenic and cytotoxic adducts from O 6 -guanine in DNA, the preferred point of attack of many carcinogens (i.e. methylnitrosourea) and alkylating chemotherapeutic agents (i.e. BCNU, temozolamide, etc.). Hypermethylation of the CpG island located in the promoter region of MGMT is primarily responsible for the loss of MGMT function in many tumor types. The methylation-mediated silencing of MGMT has two consequences for cancer. First, tumors with MGMT methylation have a new mutator phenotype characterized by the generation of transition point mutations in genes involved in cancer etiology, such as the tumor suppressor p53 and the oncogene K-ras. Second, MGMT hypermethylation demonstrates the possibility of pharmacoepigenomics: methylated tumors are more sensitive to the killing effects of alkylating drugs used in chemotherapy. These recent results underscore the importance of MGMT in basic and translational cancer research.

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“…31 SPARC clustered with collagens, whose expression was specifically enhanced in ADC and SCC, as well as genes involved in the defense response and proteolysis. Previous gene expression profiling of SCC has similarly shown SPARC and COL1A2 clustering next to each other.…”

Section: Cluster Analysis Of Genesmentioning

confidence: 99%

Gene expression profiling of esophageal cancer: Comparative analysis of Barrett's esophagus, adenocarcinoma, and squamous cell carcinoma

Greenawalt¹,

Duong²,

Smyth³

et al. 2007

Intl Journal of Cancer

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Esophageal cancer is a particularly aggressive tumor with poor prognosis, however, our current knowledge of the genes and pathways involved in tumorigenesis of the esophagus are limited. To obtain insight into the molecular processes underlying tumorigenesis of the esophagus, we have used cDNA microarrays to compare the gene expression profiles of 128 tissue samples representing the major histological subtypes of esophageal cancer (squamous cell carcinoma and adenocarcinoma (ADC)) as well as Barrett's esophagus (BE), the precursor lesion to ADC, and normal esophageal epithelium. Linear discriminant analysis and unsupervised hierarchical clustering show the separation of samples into 4 distinct groups consistent with their histological subtype. Differentially expressed genes were identified between each of the tissue types. Comparison of gene ontologies and gene expression profiles identified gene profiles specific to esophageal cancer, as well as BE. “Esophageal cancer clusters,” representing proliferation, immune response, and extracellular matrix genes were identified, as well as digestion, hydrolase, and transcription factor clusters specific to the columnar phenotype observed during BE and esophageal ADC. These clusters provide valuable insight into the molecular and functional differences between normal esophageal epithelium, BE, and the 2 histologically distinct forms of esophageal cancers. Our thorough, unbiased analysis provides a rich source of data for further studies into the molecular basis of tumorigenesis of the esophagus, as well as identification of potential biomarkers for early detection of progression. © 2007 Wiley‐Liss, Inc.

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Differential SPARC mRNA expression in Barrett's oesophagus

Cited by 36 publications

References 22 publications

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants

Distinctive activation patterns in constitutively active and gefitinib-sensitive EGFR mutants

Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer

Gene expression profiling of esophageal cancer: Comparative analysis of Barrett's esophagus, adenocarcinoma, and squamous cell carcinoma

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