Estradiol increases the secretion by MCF7 cells of several lysosomal pro-enzymes.
The synthesis and secretion of pro-cathepsin D is increased by estrogens in MCF7 cells. We quantified the effect of estradiol on other lysosomal enzymes in order to investigate the mechanism of this hypersecretion. Precursors of beta-hexosaminidase, cathepsin B and beta-galactosidase, which are routed to lysosomes via the mannose-6-phosphate (Man-6-P) receptor, were secreted in much lower amounts than pro-cathepsin D, but their secretion was also increased by estradiol. The activity of acid phosphatase, which is routed to lysosomes via a different transmembrane mechanism, was not altered by estradiol. While estradiol stimulated gene expression of pro-cathepsin D, it had no effect on that of pro-cathepsin B. We conclude that estradiol stimulates the secretion of several lysosomal pro-enzymes in MCF7 cells, suggesting that a general mechanism is responsible for this derouting rather than a specific alteration of cathepsin D structure.
Capony
F
F
INSERM U 148, Unit Hormones and Cancer, Montpellier, France.
Rougeot
C
C
Cavailles
V
V
Rochefort
H
H
D001943:Breast Neoplasms; D002460:Cell Line; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000096:biosynthesis* / Q000378:metabolism; D007700:Kinetics; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008970:Molecular Weight; D010750:Phosphoproteins / Q000096:biosynthesis / Q000302:isolation & purification; D010766:Phosphorylation
D004792:Enzyme Precursors; D010750:Phosphoproteins; D004958:Estradiol; D006867:Hydrolases