Identification and regulation of insulin-like growth factor binding proteins produced by hormone-dependent and -independent human breast cancer cell lines.
Using molecular hybridization, ligand blotting and immunoprecipitation, our studies were designed to identify the insulin-like growth factor binding proteins (IGFBPs) produced by human breast cancer cells in culture and evaluate their regulation by estradiol (E2) and polyamines (PA). We demonstrate that the hormone-dependent MCF-7 and -independent BT-20 cell lines express the mRNA for IGFBP-2 (1.7 kb) and secrete this BP (31 kDa) in the conditioned medium. In contrast, the hormone-independent MDA-MB-231 cell line does not express the IGFBP-2 gene, while synthesizing and secreting IGFBP-1. E2 administration (10(-9) M) did not significantly influence IGFBPs secretion in MCF-7 cells. Addition of alpha-difluoromethylornithine (DFMO, 4 mM), an inhibitor of PA biosynthesis, consistently lowered IGFBP-2 mRNA in the MCF-7 and BT-20 cell lines and IGFBP-1 mRNA in MDA-MB-231 cells. Surprisingly, however, this compound either did not influence IGFBPs secretion in MCF-7 cells or actually increased their secretion in the BT-20 and MDA-MB-231 cell lines. PA involvement in IGFBPs production by breast cancer cells is complex and may involve differential regulation of transcriptional and post-translational events.
Kim
I
I
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033.
Manni
A
A
Lynch
J
J
Hammond
J M
JM
D001943:Breast Neoplasms / Q000473:pathology*; D002277:Carcinoma / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D000518:Eflornithine / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D011073:Polyamines / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000378:metabolism
D002352:Carrier Proteins; D018969:Insulin-Like Growth Factor Binding Proteins; D011073:Polyamines; D012334:RNA, Neoplasm; D004958:Estradiol; D000518:Eflornithine