MODULATION OF CATHEPSIN-D AND PS2 PROTEIN-LEVELS IN HUMAN BREAST-CANCER CELL-LINES

Cathepsin-D and pS2 are two estrogen-regulated proteins in human breas t cancer cell lines. They have been considered possible prognostic fac tors in breast cancer, but results have been contradictory. To better understand the regulation of these proteins, we investigated the role of estradiol (E(2)), serum, and growth factors in hormone-dependent (M CF-7, ZR75.1) and hormone-independent (MDAMB-231, BT20) breast cancer cell lines. E(2) treatment in serum-free conditions increased intracel lular and secreted levels of pS2 in ZR75.1 and in MCF-7, secreted leve ls only of cathepsin-D in MCF-7, and both levels of cathepsin-D in ZR7 5.1. Insulin-like growth factor I (IGF-I) and progesterone receptors w ere also stimulated by E(2), whereas the estrogen receptor was down-re gulated. Following treatment with epidermal growth factor (EGF), secre ted pS2 levels doubled only in MCF-7 cells. IGF-I did not modify cathe psin-D or pS2 levels in either cell line, but caused an increase in it s own receptor. Cathepsin-D and pS2 doubled in MCF-7 cells grown in me dium supplemented with denaturated serum, but estrogen regulation of t hese proteins was still maintained. Cathepsin-D was expressed in MDAMB -231 and BT20, but its levels were modified by neither E(2) nor growth factor treatment. Conversely, neither cell line expressed detectable levels of pS2 before or after treatment. In conclusion, our results sh ow that in different types of breast cancer cells, some estrogen-regul ated proteins (e.g. pS2) are also regulated by growth factors such as EGF and other unknown serum factors. This may account for the contradi ctory results obtained regarding the prognostic relevance of cathepsin -D and pS2.