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 ca ncer cells, and tamoxifen-resistant (ZR-75-9a1) and estrogen-independe nt (ZR-PR-LT) variants was examined by electrophoresis of labeled prot eins 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 estr ogen-inducible. Treatment of ZR-75-9a1 cells with 17 beta-estradiol (E 2) and the progestin ORG 2058 increased secretion of the 52 kDa protei n; ZR-PR-LT cells were unaffected. Western blotting showed that each c ell line expressed high levels of the 52 kDa and 34 kDa forms of cathe psin D but that relatively little was being secreted. Each cell line s ecreted 52 kDa procathepsin D, but 34 kDa mature-cathepsin D was not d etected as a secreted protein. ZR-75-1 cells expressed and secreted th e highest levels of cathepsin D while ZR-75-9a1 cells expressed and se creted the least.