Estradiol stimulates cell growth and secretion of procathepsin D and a 120-kilodalton protein in the human ovarian cancer cell line BG-1.
Ovarian cancers are highly invasive. In a first attempt to define the hormones and factors involved in the control of tumor invasion and metastasis, we have used the human ovarian cancer cell line BG-1 which contains both estrogen and progesterone receptors. Protein synthesis and secretion was assayed by [35S]methionine incorporation and polyacrylamide gel electrophoresis followed by fluorography. Three responses to estradiol were found: 1) procathepsin D secretion was increased, whereas the corresponding intracellular proteins were not significantly affected; 2) an abundant but nonidentified 120-kilodalton (kDa) estrogen-induced secreted glycoprotein, different from CA125, was detected for the first time; and 3) the number of cells as determined by DNA assay was markedly stimulated, reaching a higher level of confluency. The antiestrogen OH-tamoxifen was weakly agonist at low concentrations to stimulate cell growth but was a pure antagonist on the 120-kDa protein. The steroid specificity of these responses strongly suggests that they are mediated by the estrogen receptor. We conclude that cathepsin D secretion is specifically stimulated by estrogen in this ovarian cancer cell line as it is in estrogen receptor-positive breast cancer cells. Both cathepsin D and a newly described 120-kDa secreted glycoprotein are potential markers of hormone responsiveness and/or aggressiveness which deserve to be further studied in clinical ovarian cancers.
Galtier-Dereure
F
F
Unité Hormones et Cancer (U 148), INSERM, Montpellier, France.
Capony
F
F
Maudelonde
T
T
Rochefort
H
H
D002402:Cathepsin D / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D013196:Dihydrotestosterone / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004792:Enzyme Precursors / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D006801:Humans; D008970:Molecular Weight; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D011233:Precipitin Tests; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D004792:Enzyme Precursors; D004965:Estrogen Antagonists; D011506:Proteins; D013196:Dihydrotestosterone; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; C058345:procathepsin D; D002402:Cathepsin D