Identification of genes whose expression is upregulated in lung adenocarcinoma cells in comparison with type II alveolar cells and bronchiolar epithelial cells in vivo.
To identify genes whose expression is upregulated in lung adenocarcinoma (AdC) cells in comparison with noncancerous peripheral lung epithelial cells, type II alveolar cells and bronchiolar epithelial cells, as well as AdC cells, were isolated by laser capture microdissection, and subjected to cDNA microarray analysis of 637 human cancer-related genes. Each of the component cells was obtained from several different individuals and analysed independently. As a comparison, two lung AdC cell lines and two primarily cultured normal lung epithelial cell lines were also subjected to cDNA microarray analysis. Four genes, TOP2A, MMP15, MX2 and KOC1, were commonly upregulated in microdissected AdC cells in comparison with microdissected epithelial cells. Hierarchical clustering analysis revealed that differences in gene-expression profiles were more evident between cultured and uncultured cells than between cancerous and noncancerous cells. To further identify the common molecular targets of AdC cells in vivo, quantitative real-time RT-PCR was performed against the four genes upregulated by cDNA microarray analysis. The TOP2A, MMP15, MX2 and KOC1 genes were overexpressed in 10/10 (100%), 8/10 (80%), 5/10 (50%) and 3/10 (30%) microdissected AdC cell samples, respectively, in comparison with any of nine independently microdissected noncancerous epithelial cell samples. The TOP2A gene was commonly overexpressed in lung AdC cells, as previously reported. In addition, the MMP15 and MX2 genes were identified, for the first time, as being commonly overexpressed in lung AdC cells. These results strongly indicate that the MMP15 and MX2 genes could be novel markers for molecular diagnosis and therapy of lung AdC.
Kobayashi
Keiko
K
Biology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan.
Nishioka
Michiho
M
Kohno
Takashi
T
Nakamoto
Masaki
M
Maeshima
Arafumi
A
Aoyagi
Kazuhiko
K
Sasaki
Hiroki
H
Takenoshita
Seiichi
S
Sugimura
Haruhiko
H
Yokota
Jun
J
D000230:Adenocarcinoma / Q000235:genetics*; D000951:Antigens, Neoplasm; D001483:Base Sequence; D001980:Bronchi / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D017931:DNA Primers; D004250:DNA Topoisomerases, Type II / Q000235:genetics; D004268:DNA-Binding Proteins; D019204:GTP-Binding Proteins / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics*; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000235:genetics; D064547:Myxovirus Resistance Proteins; D009363:Neoplasm Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D011650:Pulmonary Alveoli / Q000502:physiology*; D020545:Respiratory Mucosa / Q000502:physiology*
D000951:Antigens, Neoplasm; D017931:DNA Primers; D004268:DNA-Binding Proteins; C507098:MMP15 protein, human; D064547:Myxovirus Resistance Proteins; D009363:Neoplasm Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D053517:Matrix Metalloproteinase 15; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D019204:GTP-Binding Proteins; D004250:DNA Topoisomerases, Type II; C000618811:TOP2A protein, human