Identification of genes associated with enhanced metastasis of a large cell lung carcinoma cell line.
We have compared the transcriptional profile of large cell lung tumor cell lines NIH-H460 and H460-M making use of the Affymetrix GeneChip system. H460-M is derived from NIH-H460 and displays enhanced experimental and spontaneous metastasis in nude mice. Out of the 12,600 genes investigated, 73 (0.6%) were up-regulated and 114 (0.9%) were down-regulated on the basis of the scoring criteria. We have classified the de-regulated genes according to the following categories: immune response, enzymes, modulation of transcription, signal transduction, cytoskeleton/adhesion and extracellular matrix associated proteins, cell-cycle/apoptosis, transporters and 'others'. Among the remarkable features of this system are the up-regulation of the steady-state mRNA levels of neuroendocrine markers such as neurotensin (NTS), neuroendocrine-specific protein (NSP), neural cell adhesion molecule 1 (NCAM1) and gamma-aminobutyric acid B-type receptor (GPR51) in cell line H460-M. Semaphorin 3B (SEMA3B) was dramatically down-regulated in cell line H460-M and emerged as the most interesting gene for target validation.
de Lange
Robert
R
Roche Diagnostics GmbH, Division Pharma, D-82372 Penzberg, Germany.
Dimoudis
Nikolaos
N
Weidle
Ulrich H
UH
D018287:Carcinoma, Large Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C539821:NR4A1 protein, human; C539882:NR4A2 protein, human; C490412:NR4A3 protein, human; D009419:Nerve Tissue Proteins; C539818:Nr4a1 protein, mouse; C539883:Nr4a2 protein, mouse; D009687:Nuclear Proteins; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D057126:Nuclear Receptor Subfamily 4, Group A, Member 2; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D011988:Receptors, Thyroid Hormone; D014157:Transcription Factors