Growth of human breast cancer cell lines is inhibited by the somatostatin analog BIM23014.
Somatostatin has been shown to lower plasma levels of various hormones and growth factors involved in regulation of the growth of human breast cells. In the present study we examined the ability of the somatostatin octapeptide analog BIM23014 to modulate the in vitro growth of five human breast cell lines: HBL100, Hs578T, MDAMB231, T47D, and MCF7. BIM23014 inhibited the growth of the two steroid-dependent cell lines, MCF7 and T47D, in a dose-related manner. This inhibitory effect was only observed when MCF7 and T47D cells were cultivated in medium containing steroid-depleted serum. The growth of a MCF7 variant capable of growth in serum-free medium was also inhibited by BIM23014, indicating that serum factors are not required for this inhibition. In the serum-free medium, the addition of estradiol before or during treatment with BIM23014 abolished its inhibitory effects on cell growth. The studies including time course, competitive inhibition, and cross-linking of iodinated BIM23014 to its receptor revealed a specific binding on MCF7 cells and showed a single 57,000 mol wt protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results support the hypothesis that BIM23014 inhibits the growth of steroid-receptor positive cells of human breast cancers through its own receptor in estradiol-free conditions.
Prévost
G
G
Institut d'Oncologie Cellulaire et Moléculaire Humaine, Bobigny, France.
Foehrlé
E
E
Thomas
F
F
Pihan
I
I
Veber
N
N
Starzec
A
A
Israël
L
L
D001667:Binding, Competitive; D001769:Blood; D001943:Breast Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D003432:Cross-Linking Reagents; D003470:Culture Media; D004247:DNA / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D013004:Somatostatin / Q000031:analogs & derivatives*; D014407:Tumor Cells, Cultured
D003432:Cross-Linking Reagents; D003470:Culture Media; D007328:Insulin; D010456:Peptides, Cyclic; C060347:lanreotide; D011374:Progesterone; D004958:Estradiol; D013004:Somatostatin; D004247:DNA