Processing of insulin-like growth factor-II (IGF-II) by human breast cancer cells.
MCF-7 cells transfected with human prepro-IGF-II cDNA secreted two large precursor forms of 22 and 15 kDa, with trace amounts of the mature 7 kDa IGF-II, suggesting that overexpression leads to saturation of processing and the secretion of precursors. The 15 kDa form was separated from 22 and 7 kDa IGF-II by cation-exchange chromatography. Intracellular IGF-II, detectable only in detergent buffers, existed in two forms of 24 and 22 kDa. Conditioned media from four other breast cancer cell lines (MDA-231, HBL-100, T47D and MCF-7 McG), all contained mature 7 kDa IGF-II with trace amounts (< 10%) of the 15 kDa IGF-II. Oestradiol induced IGF-II secretion in oestrogen-sensitive MCF-7 and T47D cells, but secretion was constitutively higher in oestrogen-unresponsive MDA-231 and HBL-100 cells. This indicates, for the first time, that oestrogen regulation of IGF-II peptide in breast cancer cells, and expression throughout all cell lines tested, would support the hypothesis that IGF-II has an autocrine regulatory function in breast cancer.
Lee
A V
AV
Imperial Cancer Research Fund, Breast Biology Group, School of Biological Sciences, University of Surrey, Guildford, UK.
Darbre
P
P
King
R J
RJ
D002852:Chromatography, Ion Exchange; D017077:Culture Media, Conditioned; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004958:Estradiol / Q000494:pharmacology; D015870:Gene Expression; D006801:Humans; D015151:Immunoblotting; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D011498:Protein Precursors / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology
D017077:Culture Media, Conditioned; D004273:DNA, Neoplasm; D011498:Protein Precursors; D004958:Estradiol; D007335:Insulin-Like Growth Factor II; D015032:Zinc