Regulation of insulin-like growth factor binding proteins in ovarian cancer cells by oestrogen.
Insulin-like growth factor-I (IGF-I), its receptor and its binding proteins are expressed by ovarian cancer cells. In this study, we examined oestradiol (E2) regulation of IGF-I and IGF binding proteins (IGFBP) in an oestrogen-responsive ovarian cancer cell line, PE04. In serum-free conditions, PE04 cell monolayer growth was increased 1.64-fold by 3 nmol/l E2 compared with controls, although IGF-I mRNA levels were not increased. In contrast to IGF-I mRNA, IGFBP mRNA was regulated by E2. E2 caused a marked decrease in IGFBP-3 RNA, but IGFBP-2, -4 and -6 levels were only minimally depressed. IGFBP-5 mRNA levels were increased by E2. Tamoxifen had less effect on IGFBP mRNA regulation. Ligand blotting showed that E2 reduced IGFBP levels in conditioned media. IGFBP RNA was also detected in human ovarian tissue samples. Thus, IGFBP expression can be regulated in oestrogen-responsive ovarian cancer by E2.
Krywicki
R F
RF
Brooke Army Medical Center, Hematology/Oncology Service, Ft. Sam Houston, Texas 78234.
Figueroa
J A
JA
Jackson
J G
JG
Kozelsky
T W
TW
Shimasaki
S
S
Von Hoff
D D
DD
Yee
D
D
D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D013002:Somatomedins / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D013002:Somatomedins; D013629:Tamoxifen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1