Inhibition of growth of prostatic cancer cell lines by peptide analogues of insulin-like growth factor 1.
We have investigated three prostatic cancer cell lines, PC-3, DU-145, and LNCa.FGC, and found that all three cell lines can grow in serum-free medium without the addition of exogenous growth factors. All three cell lines produce substantial amounts of insulin-like growth factor 1 (IGF-1) that is secreted in the medium and they all display constitutively autophosphorylated IGF-1 receptors; two of the cell lines overexpress IGF-1 receptor RNA. The growth of all three cell lines is inhibited by an antisense oligodeoxynucleotide to IGF-1 receptor RNA or by peptide analogues of IGF-1 that compete with IGF-1 binding to its receptor. Our results indicate that these three cell lines grow by an autocrine loop in which the overproduced IGF-1 activates its receptor. Interference with the activation of the receptor leads to cessation of growth.
Pietrzkowski
Z
Z
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Mulholland
G
G
Gomella
L
L
Jameson
B A
BA
Wernicke
D
D
Baserga
R
R
D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000031:analogs & derivatives / Q000494:pharmacology*; D008297:Male; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000473:pathology*; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016376:Oligonucleotides, Antisense; D010455:Peptides; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1