Reduced levels of cathepsin D associated with tamoxifen resistance and estrogen independence in the ZR-75-1 human breast cancer cell line.
The expression and secretion of cathepsin D by ZR-75-1 human breast cancer cells, and tamoxifen-resistant (ZR-75-9a1) and estrogen-independent (ZR-PR-LT) variants was examined by electrophoresis of labeled proteins and Western blotting. Secreted proteins of 160 kDa, 52 kDa and 34 kDa were identified, and in ZR-75-1 cells, they were shown to be estrogen-inducible. Treatment of ZR-75-9a1 cells with 17 beta-estradiol (E2) and the progestin ORG 2058 increased secretion of the 52 kDa protein; ZR-PR-LT cells were unaffected. Western blotting showed that each cell line expressed high levels of the 52 kDa and 34 kDa forms of cathepsin D but that relatively little was being secreted. Each cell line secreted 52 kDa procathepsin D, but 34 kDa mature-cathepsin D was not detected as a secreted protein. ZR-75-1 cells expressed and secreted the highest levels of cathepsin D while ZR-75-9a1 cells expressed and secreted the least.
Long
B J
BJ
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, NY 10595, USA.
van den Berg
H W
HW
D001943:Breast Neoplasms; D002402:Cathepsin D / Q000096:biosynthesis / Q000378:metabolism*; D002460:Cell Line; D002999:Clone Cells; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000032:analysis; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008970:Molecular Weight; D011282:Pregnenediones / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013629:Tamoxifen / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D011282:Pregnenediones; D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D004958:Estradiol; D066246:ErbB Receptors; D002402:Cathepsin D