TY - JOUR
T1 - A novel target gene, SKP2, within the 5p13 amplicon that is frequently detected in small cell lung cancers
AU - Yokoi, Sana
AU - Yasui, Kohichiroh
AU - Saito-Ohara, Fumiko
AU - Koshikawa, Katsumi
AU - Iizasa, Toshihiko
AU - Fujisawa, Takehiko
AU - Terasaki, Takeo
AU - Horii, Akira
AU - Takahashi, Takashi
AU - Hirohashi, Setsuo
AU - Inazawa, Johji
N1 - Funding Information:
Supported by Grants-in-Aid for Cancer Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; and from the Ministry of Health, Labour, and Welfare, Japan.
Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.
PY - 2002
Y1 - 2002
N2 - 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 p27KIP1, 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 p27KIP1 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.
AB - 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 p27KIP1, 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 p27KIP1 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.
UR - http://www.scopus.com/inward/record.url?scp=0036309975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036309975&partnerID=8YFLogxK
U2 - 10.1016/S0002-9440(10)64172-7
DO - 10.1016/S0002-9440(10)64172-7
M3 - Article
C2 - 12107105
AN - SCOPUS:0036309975
VL - 161
SP - 207
EP - 216
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 1
ER -