Castagnetta L A, Granata O M, Farruggio R, Cannella S, Montesanti A, Oliveri G, Sorci C, Mesiti M, Carruba G
Hormone Biochemistry Laboratories, University Medical School, Policlinico, Palermo, Italy.
J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):367-74. doi: 10.1016/0960-0760(95)00081-a.
In order to measure the formation and degradation rates of estradiol by human breast cancer cells, after assessing the biochemical basis of hormone responsiveness and growth response to estrogens, we considered both responsive, estrogen receptor (ER) positive, and non-responsive, ER-negative, breast cancer cell lines, i.e. MCF7, ZR75-1 and MDA-MB231. To this end, we employed a novel "intact cell" approach which allows us, after 24 h incubation, to analyze several enzyme activities in sequence, concurrently with the monitoring of labeled precursor degradation. Our investigations led to the following evidence: (a) the reductive activity of the 17 beta-hydroxysteroid oxoreductase (17 beta-HSOR) appears to be higher than the oxidative only in responsive, ER-rich MCF7 and ZR75-1 cells, as also previously observed by others; (b) this activity is, on the contrary, much lower in MDA-MB231 cells and other unresponsive, ER-poor breast cancer cell lines; (c) conversely, the oxidative activity shows an opposite pattern, being limited in MCF7 and ZR75-1 cells and much higher in MDA-MB231 cells. Overall, a 17 beta-HSOR reductive pathway prevails in both MCF7 and ZR75-1 cells, whilst the oxidative pathway is prevalent in MDA-MB231 cells, leading to a large formation of estrone that is no further metabolized, at least in the experimental conditions used. Our results may provide a likely explanation of previous data on the different estrogen content of breast tumor tissues.
为了测量人乳腺癌细胞中雌二醇的生成和降解速率，在评估激素反应性和雌激素生长反应的生化基础后，我们考虑了雌激素受体（ER）阳性的反应性和ER阴性的无反应性乳腺癌细胞系，即MCF7、ZR75-1和MDA-MB231。为此，我们采用了一种新颖的“完整细胞”方法，该方法使我们在孵育24小时后，能够依次分析几种酶活性，同时监测标记前体的降解。我们的研究得出了以下证据：（a）17β-羟基类固醇氧化还原酶（17β-HSOR）的还原活性似乎仅在反应性、富含ER的MCF7和ZR75-1细胞中高于氧化活性，正如其他人之前所观察到的；（b）相反，这种活性在MDA-MB231细胞和其他无反应性、ER含量低的乳腺癌细胞系中要低得多；（c）相反，氧化活性呈现相反的模式，在MCF7和ZR75-1细胞中受到限制，而在MDA-MB231细胞中要高得多。总体而言，17β-HSOR还原途径在MCF7和ZR75-1细胞中均占主导地位，而氧化途径在MDA-MB231细胞中占主导地位，导致大量雌酮生成，至少在所使用的实验条件下不再进一步代谢。我们的结果可能为先前关于乳腺肿瘤组织中不同雌激素含量的数据提供一个合理的解释。
