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.
Wada
Tomoaki
T
Division of Functional Genomics, School of Medicine, Jichi Medical University, Tochigi, Japan.
Yamashita
Yoshihiro
Y
Saga
Yasushi
Y
Takahashi
Kayoko
K
Koinuma
Koji
K
Choi
Young Lim
YL
Kaneda
Ruri
R
Fujiwara
Shin-Ichiro
S
Soda
Manabu
M
Watanabe
Hideki
H
Kurashina
Kentaro
K
Hatanaka
Hisashi
H
Enomoto
Munehiro
M
Takada
Shuji
S
Mano
Hiroyuki
H
Suzuki
Mitsuaki
M
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