Adams J B, Phillips N S, Pewnim T
School of Biochemistry, University of New South Wales, Syndey, Australia.
J Steroid Biochem. 1989 Oct;33(4A):637-42. doi: 10.1016/0022-4731(89)90053-8.
A positive correlation between the expression of estrogen sulphotransferase (EC 2.8: 2.4) and the estrogen receptor (ER) in human breast cancer tissues was previously demonstrated. We have now established that a similar correlation exists between the expression of hydroxysteroid sulphotransferase (EC 2.8: 2.2) and ER in such tissues. Enzyme activity was present in 93% of the ER + tumor cytosols (mean 59 +/- 44 (SD) pmol dehydroepiandrosterone sulphate formed per mg protein per 2 h (n = 42). Activity was detected in 68% of ER - tumors and this was significantly lower (mean 21 +/- 26 (SD) (n = 19), P less than 0.001) than the former group. Metabolism of estradiol-17 beta (E2) and the adrenal-derived estrogen 5-androstene-3 beta, 17 beta-diol (ADIOL), which is a substrate for hydroxysteroid sulphotransferase but not estrogen sulphotransferase, was studied in four ER + human mammary cancer cell lines (MCF-7, T47-D, MDA-MB-361 and ZR-75-1) and four ER-human mammary cell lines (BT-20, MDA-MB-231, MDA-MB-330 and HBL-100), employing steroid concentrations of 1 nM. At this concentration, formation of ester sulphates was a major route of metabolism in the ER + cell lines; E2 yielding a mean of 6.5 pmol estrogen monosulphates/mg DNA in 16 h and ADIOL yielding a mean of 9.4 pmol C19-5-ene steroid monosulphates/mg DNA in 16 h. In three of the four ER - cell lines, formation of sulphates from E2 occurred at an eight-fold lower rate (mean 0.8 pmol estrogen sulphates/mg DNA in 16 h), whereas MDA-MB-330 cells did not form estrogen sulphates. Only one of the four ER- cell lines (BT-20) sulphurylated ADIOL and this was at a 12-fold lower rate compared to the mean value for the ER + cel lines. Oxidation of E2 and ADIOL occurred in all cell lines and was generally the major route of metabolism in the ER - cells. A significant correlation between formation of estrone and dehydroepiandrosterone occurred for all cell lines (r = 0.98, P less than 0.001) indicating that the same 17 beta-hydroxysteroid dehydrogenase was probably involved. Since ADIOL is estrogenic in a number of systems at the concentration found in the blood of Western women (approximately 2 nM), the coordinated expression of hydroxysteroid sulphotransferase, estrogen sulphotransferase, and ER, supports the concept of a functional relationship between estrogen action via ER and sulphurylation reactions.
先前已证实，人乳腺癌组织中雌激素硫酸转移酶（EC 2.8: 2.4）的表达与雌激素受体（ER）之间存在正相关。我们现已确定，此类组织中羟类固醇硫酸转移酶（EC 2.8: 2.2）的表达与ER之间也存在类似的相关性。93%的ER +肿瘤细胞溶质中存在酶活性（平均每毫克蛋白质每2小时形成59±44（标准差）皮摩尔硫酸脱氢表雄酮，n = 42）。在68%的ER -肿瘤中检测到活性，且该活性明显低于前一组（平均21±26（标准差），n = 19，P < 0.001）。在四种ER +人乳腺癌细胞系（MCF-7、T47-D、MDA-MB-361和ZR-75-1）和四种ER -人乳腺细胞系（BT-20、MDA-MB-231、MDA-MB-330和HBL-100）中，采用1 nM的类固醇浓度，研究了雌二醇-17β（E2）和肾上腺源性雌激素5-雄烯-3β,17β-二醇（ADIOL）的代谢情况，ADIOL是羟类固醇硫酸转移酶的底物，但不是雌激素硫酸转移酶的底物。在此浓度下，硫酸酯的形成是ER +细胞系中的主要代谢途径；E2在16小时内产生平均6.5皮摩尔雌激素单硫酸盐/毫克DNA，ADIOL在16小时内产生平均9.4皮摩尔C19-5-烯类固醇单硫酸盐/毫克DNA。在四种ER -细胞系中的三种中，E2形成硫酸盐的速率低八倍（平均16小时内0.8皮摩尔雌激素硫酸盐/毫克DNA），而MDA-MB-330细胞不形成雌激素硫酸盐。四种ER -细胞系中只有一种（BT-20）能使ADIOL硫酸化，且与ER +细胞系的平均值相比，其速率低12倍。所有细胞系中均发生E2和ADIOL的氧化，且在ER -细胞中通常是主要的代谢途径。所有细胞系中雌酮和脱氢表雄酮的形成之间存在显著相关性（r = 0.98，P < 0.001），表明可能涉及相同的17β-羟类固醇脱氢酶。由于在西方女性血液中发现的浓度（约2 nM）下，ADIOL在许多系统中具有雌激素活性，羟类固醇硫酸转移酶、雌激素硫酸转移酶和ER的协同表达支持了通过ER的雌激素作用与硫酸化反应之间存在功能关系的概念。
