Estrogen and insulin modulation of intracellular insulin-like growth factor binding proteins in human breast cancer cells: possible involvement in lysosomal hydrolases oversecretion.
Differences in insulin-like growth factor binding proteins (IGFBPs) expressed within estrogen receptor positive (ER+, MCF-7/6) and negative (ER-, MDA-MB-231) human breast cancer cells cultured in chemically defined medium were observed. In the absence of insulin, 17 beta-estradiol affects this expression in ER+ cells by significantly reducing 34 and 28 kDa species. In ER+ cells, insulin appears to minimize the estrogen induced reduction of these 34 and 28 kDa IGFBPs and stimulates a 24 kDa type. We suggest that through its association with a given IGFBP, insulin-like growth factor-II (IGF-II) directs lysosomal enzymes to secretion by its binding to the mannose-6-phosphate/IGF-II receptors present in the Golgi apparatus. Alternatively, the association of IGF-II with another IGFBP would inhibit this binding and lead to its autocrine or intracrine mitogenic action via the IGF-I receptor.
Dubois
V
V
Laboratoire de Biologie Cellulaire, University of Louvain, Louvain-la-Neuve, Belgium.
Couissi
D
D
Schonne
E
E
Schneider
Y J
YJ
Remacle
C
C
Trouet
A
A
D001943:Breast Neoplasms / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004967:Estrogens / Q000502:physiology*; D006801:Humans; D006867:Hydrolases / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D018969:Insulin-Like Growth Factor Binding Proteins; D008247:Lysosomes / Q000201:enzymology*; D011960:Receptors, Estrogen / Q000378:metabolism; D013002:Somatomedins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D004967:Estrogens; D007328:Insulin; D018969:Insulin-Like Growth Factor Binding Proteins; D011960:Receptors, Estrogen; D013002:Somatomedins; D006867:Hydrolases