A novel target gene, SKP2, within the 5p13 amplicon that is frequently detected in small cell lung cancers.
We investigated DNA copy-number aberrations in 22 cell lines derived from small cell lung cancers (SCLCs) using comparative genomic hybridization. A minimal common region at 5p13, within the 5p11-p13 amplicon that was most frequently involved, harbored the CDH6, PC4, and SKP2 genes. These three genes showed amplification and consequent overexpression in the SCLC cell lines. SKP2 positively regulates progression of cell cycle by targeting several regulators, such as the cell-cycle inhibitor p27(KIP1), for ubiquitin-mediated degradation. SKP2 was amplified in 7 (44%) of 16 primary SCLC tumors, and consequently overexpressed in 10 (83%) of the 12 of those tumors we examined. Expression levels of SKP2 protein were cell cycle-dependent in SCLC cells as well as in normal cells, and were correlated with the DNA copy-number of the gene. There was an inverse correlation between the expression of SKP2 and p27(KIP1) proteins. Down-regulation of SKP2 using an anti-sense oligonucleotide remarkably suppressed the growth of SCLC cells. Our results indicate that SKP2 is likely to be a target of the 5p13 amplification and to play an important role in the growth of SCLC cells.
Yokoi
Sana
S
Department of Molecular Cytogenetics, Medical Research Institute, Tokyo Medical and Dental University, Tokyo, Japan.
Yasui
Kohichiroh
K
Saito-Ohara
Fumiko
F
Koshikawa
Katsumi
K
Iizasa
Toshihiko
T
Fujisawa
Takehiko
T
Terasaki
Takeo
T
Horii
Akira
A
Takahashi
Takashi
T
Hirohashi
Setsuo
S
Inazawa
Johji
J
D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000235:genetics; D005784:Gene Amplification; D018628:Gene Dosage; D015870:Gene Expression; D016678:Genome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D020320:Oligoribonucleotides, Antisense / Q000494:pharmacology; D044786:S-Phase Kinase-Associated Proteins
D018797:Cell Cycle Proteins; D020320:Oligoribonucleotides, Antisense; D044786:S-Phase Kinase-Associated Proteins; D004247:DNA