Cappelletti V, Fioravanti L, Miodini P, Di Fronzo G
Oncologia Sperimentale C, Instituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
Tumour Biol. 1996;17(5):290-8. doi: 10.1159/000217991.
Cathepsin-D and pS2 are two estrogen-regulated proteins in human breast cancer cell lines. They have been considered possible prognostic factors in breast cancer, but results have been contradictory. To better understand the regulation of these proteins, we investigated the role of estradiol (E2), serum, and growth factors in hormone-dependent (MCF-7, ZR75.1) and hormone-independent (MDAMB-231, BT20) breast cancer cell lines. E2 treatment in serum-free conditions increased intracellular and secreted levels of pS2 in ZR75.1 and in MCF-7, secreted levels only of cathepsin-D in MCF-7, and both levels of cathepsin-D in ZR75.1. Insulin-like growth factor I (IGF-I) and progesterone receptors were also stimulated by E2, whereas the estrogen receptor was down-regulated. Following treatment with epidermal growth factor (EGF), secreted pS2 levels doubled only in MCF-7 cells. IGF-I did not modify cathepsin-D or pS2 levels in either cell line, but caused an increase in its own receptor. Cathepsin-D and pS2 doubled in MCF-7 cells grown in medium supplemented with denaturated serum, but estrogen regulation of these proteins was still maintained. Cathepsin-D was expressed in MDAMB-231 and BT20, but its levels were modified by neither E2 nor growth factor treatment. Conversely, neither cell line expressed detectable levels of pS2 before or after treatment. In conclusion, our results show that in different types of breast cancer cells, some estrogen-regulated proteins (e.g. pS2) are also regulated by growth factors-such as EGF and other unknown serum factors. This may account for the contradictory results obtained regarding the prognostic relevance of cathepsin-D and pS2.
组织蛋白酶D和pS2是人类乳腺癌细胞系中两种受雌激素调节的蛋白质。它们曾被认为可能是乳腺癌的预后因素，但结果相互矛盾。为了更好地理解这些蛋白质的调节机制，我们研究了雌二醇（E2）、血清和生长因子在激素依赖性（MCF-7、ZR75.1）和激素非依赖性（MDAMB-231、BT20）乳腺癌细胞系中的作用。在无血清条件下用E2处理可增加ZR75.1和MCF-7细胞内及分泌的pS2水平，在MCF-7中仅增加组织蛋白酶D的分泌水平，在ZR75.1中则增加组织蛋白酶D的两种水平。胰岛素样生长因子I（IGF-I）和孕激素受体也受到E2的刺激，而雌激素受体则下调。用表皮生长因子（EGF）处理后，仅MCF-7细胞中分泌的pS2水平增加了一倍。IGF-I在两种细胞系中均未改变组织蛋白酶D或pS2的水平，但导致其自身受体增加。在添加了变性血清的培养基中生长的MCF-7细胞中，组织蛋白酶D和pS2增加了一倍，但这些蛋白质的雌激素调节作用仍得以维持。MDAMB-231和BT20中表达了组织蛋白酶D，但其水平不受E2或生长因子处理的影响。相反，两种细胞系在处理前后均未表达可检测水平的pS2。总之，我们的结果表明，在不同类型的乳腺癌细胞中，一些受雌激素调节的蛋白质（如pS2）也受生长因子（如EGF）和其他未知血清因子的调节。这可能解释了关于组织蛋白酶D和pS2预后相关性所获得的相互矛盾的结果。
