Insulin-like growth factor (IGF) system components in human prostatic cancer cell-lines: LNCaP, DU145, and PC-3 cells.
BACKGROUND
Evidence has been accumulating that in many tumors, insulin-like growth factors (IGFs) promote cancer cell growth in an autocrine/paracrine manner via the IGF-I receptor. In an effort to understand the role of IGFs in prostate cancer cell growth, we characterized the IGF system components produced by human prostatic cancer cell-lines, LNCaP, DU145, and PC-3, grown in serum-free medium.


METHODS
IGFs, their receptors, and IGF binding proteins (IGFBPs) produced by the three human prostate cell lines were characterized by reverse transcriptase-polymerase chain reaction (RT-PCR), radioimmunoassay (RIA), Western ligand blot, Western immunoblot, and Northern blot analyses.


RESULTS
mRNA for IGF-II and receptors for IGF-I and IGF-II were detected in all three cell-lines by RT-PCR. In contrast to the published study, only LNCaP cells expressed a trace amount of IGF-I mRNA. RIA on conditioned media collected from these cells revealed that all three cell-lines produced measurable IGF-II but not IGF-I. Western Ligand blot, Western immunoblot, and Northern blot analyses revealed that LNCaP, DU145, and PC-3 cells expressed IGFBP-2, IGFBP-2/-3/-4/-6, and IGFBP-2/-3/-4/-5/-6, respectively. IGF-II stimulated [3H]thymidine incorporation into DNA in DU145 and PC-3 cells significantly although the effect was small. DNA synthesis in PC-3 cells but not in LNCaP and DU145 cells was significantly inhibited by the IGF-I receptor-specific monoclonal antibody.


CONCLUSIONS
Theses results suggest potentially important roles of IGFs and IGFBPs in prostate cancer cell growth, and that in particular, IGF-II may play a critical role in prostate cancer cell growth.
Kimura
G
G
Department of Molecular Genetics, Beckman Research Institute of the City of Hope, Duarte, California, USA.
Kasuya
J
J
Giannini
S
S
Honda
Y
Y
Mohan
S
S
Kawachi
M
M
Akimoto
M
M
Fujita-Yamaguchi
Y
Y
D000911:Antibodies, Monoclonal; D001483:Base Sequence; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D017077:Culture Media, Conditioned / Q000737:chemistry; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000235:genetics; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000235:genetics / Q000378:metabolism; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000235:genetics / Q000378:metabolism; D018976:Insulin-Like Growth Factor Binding Protein 6 / Q000235:genetics / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000235:genetics* / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D011471:Prostatic Neoplasms; D012333:RNA, Messenger / Q000032:analysis; D017526:Receptor, IGF Type 1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000166:cytology / Q000502:physiology
D000911:Antibodies, Monoclonal; D017077:Culture Media, Conditioned; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D018976:Insulin-Like Growth Factor Binding Protein 6; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1