Changes in the secretion of insulin-like growth factor binding proteins -2 and -4 associated with the development of tamoxifen resistance and estrogen independence in human breast cancer cell lines.
We investigated the secretion of insulin-like growth factor binding proteins (IGFBPs) by estrogen-dependent ZR-75-1 and MCF-7 human breast cancer cells, and tamoxifen-resistant (ZR-75-9a1 and LY2) and estrogen-independent (ZR-PR-LT) variants which express altered levels of IGF-I receptor. IGFBP species (35 kDa and 44 kDa) were detectable in conditioned serum-free medium (SFM) by immunoblotting and positively identified as IGFBP-2 and -3, respectively. Secretion of IGFBP-2 into SFM by the tamoxifen-resistant and estrogen-independent cell lines was markedly reduced and secretion into SFM of the 24-kDa species, assigned the identity of IGFBP-4, was also reduced in the tamoxifen-resistant lines. There was no clear correlation between patterns of IGFBP secretion and IGF-I receptor expression.
Maxwell
P
P
Department of Oncology, The Queen's University of Belfast, Belfast City Hospital, UK.
van den Berg
H W
HW
D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000378:metabolism*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000378:metabolism*; D008163:Luminescent Measurements; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D012636:Secretory Rate / Q000187:drug effects; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D004967:Estrogens; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D013629:Tamoxifen