Screening for genetic abnormalities involved in ovarian carcinogenesis using retroviral expression libraries.
The purpose of this study was to screen for genes involved in ovarian carcinogenesis in an attempt to develop an effective molecular-targeted therapy for ovarian cancer. We constructed retroviral expression libraries for the human ovarian cancer cell lines SHIN-3 and TYK-CPr, and performed a focus formation assay with 3T3 cells. As a result, proteasome subunit beta-type 2 (PSMB2), ubiquitin-specific protease 14 (USP14), and keratin 8 (KRT8) were identified from SHIN-3, and polymerase II RNA subunit (POLR2E), chaperonin containing T-complex polypeptide 1 subunit 4 (CCT4), glia maturation factor beta (GMFB), and neuroblastoma ras viral oncogene homolog (NRAS) from TYK-CPr. NRAS gene analysis revealed a CAA --> AAA substitution at codon 61, resulting in a Glu --> Lys change at position 61. When the mutant NRAS was introduced into fibroblasts for its expression, many transformed foci were generated, confirming the transforming ability of the mutant NRAS.
Division of Functional Genomics, School of Medicine, Jichi Medical University, Tochigi, Japan.
Tomoaki
T
Wada
Yoshihiro
Y
Yamashita
Yasushi
Y
Saga
Kayoko
K
Takahashi
Koji
K
Koinuma
Young Lim
YL
Choi
Ruri
R
Kaneda
Shin-Ichiro
S
Fujiwara
Manabu
M
Soda
Hideki
H
Watanabe
Kentaro
K
Kurashina
Hisashi
H
Hatanaka
Munehiro
M
Enomoto
Shuji
S
Takada
Hiroyuki
H
Mano
Mitsuaki
M
Suzuki
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D005260:Female; D015723:Gene Library; D011905:Genes, ras / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics*; D012190:Retroviridae / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction