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Study Objective: We investigated the gene expression profiles of malignant pleural mesothelioma (MPM) specimens to identify novel genes that are potentially involved in the oncogenic transformation of human pleural cells.Design: Complementary DNA (cDNA) microarray transcriptional profiling studies of 10 MPM cell lines and 4 MPM primary tumor specimens were performed using hierarchic clustering. To confirm microarray data, we used real-time polymerase chain reaction and immunoblotting.Results: Cluster analysis differentiated among epithelial (E), sarcomatoid, and biphasic MPM variants. Expression profiling identified common overexpressed or underexpressed genes in MPM. Notably, matriptase messenger RNA was found to be overexpressed by 826-fold in E MPM, with protein expression subsequently confirmed by immunoblot analysis. This recently characterized trypsin-like serine protease has been implicated in tumor invasion and metastasis of E-derived cancers, but has not been described until now in MPM. We also identified other novel genes, such as insulin-like growth factor binding protein 5 and a cDNA clone similar to proteolipid MAL2.Conclusions: Thus, further large-scale profiling of MPM may elucidate previously unrecognized molecular mechanisms by identifying novel genes that are involved in malignant transformation. Our study has now found matriptase to be one of these mesothelioma-associated genes, with potential pathogenic and therapeutic significance. [ABSTRACT FROM AUTHOR]

Examines the role of activated leukocyte cell adhesion molecule and neutral cadherin in metastasis and lung microcirculation. Expression of transmembrane glycoprotein N-cadherin; Immunohistochemical staining; Homing of metastatic carcinoma to the lung.

Examines the relationship of non-small cell lung cancer gene profiles with lung development. Segregation of tumors by histology; Histology gene markers; Genetic transcription; Cell differentiation and proliferation; Cell cycle.

Reports on the identification of novel potential target molecules that modulate or inactivate disease-inducing, allergen-specific T-helper type 2 (Th2) lymphocytes. Analysis of expression of genes in the draining lymph node in a mouse model of allergic asthma using representational difference analysis of complementary DNAs.

Implicates insulin-like growth factor binding protein-3 (IGFBP-3) as a gene modulated by cyclo-oxygenase-2 (COX-2) overexpression in cancer cells. Comparison of the expression of 1,700 genes in the human lung adenocarcinoma cell line A549, transduced with COX-2, to A549 cells with either no or very little COX-2 expression.

Examines interleukin (IL) 5-regulated genes and proteins in human eosinophils. Comparison of proteomic and genomic analysis of eosinophils; Gene expression; Role of IL-5 in the biology of eosinophils.

Suggests that spotted oligonucleotide arrays are an attractive alternative to other microarray technologies and may offer significant advantages in terms of cost, ease of production, flexibility and specificity. Production of arrays by depositing 70-mer oligonucleotides on modified glass slides.

Reports that keratinocyte growth factor (KGF) stimulates the proliferation and differentiation of alveolar type II cells in vitro. Analysis of messenger RNA from type II cells that had been cultured in the presence and absence of KGF by DNA microarray analysis with Affimetrix Inc.'s gene profiling system.

Determines the transcriptional programs that are active in non-small cell lung cancer. Analysis of gene expression patterns using GeneChip microarrays that allow for the analysis of 12,000 genes in 12 non-small cell lung cancer tumor samples, 6 normal histology samples from lung resections for cancer, and pooled normal lung RNA obtained commercially.