Estrone and Dehydroepiandrosterone Sulfatase Activities and Plasma Estrone Sulfate Levels in Human Breast Carcinoma1

Home , Estrogen, Estrone, Estrone sulfate

[CANCER RESEARCH 44, 661-664, February 1984]

Odile Prost,2 Marie O. Turrel, Nicole Dahan, Christine Graveur, and GÃ©rardL.Adessi

Unite de Recherche de Biochimie Hormona/e et des Regulations, INSERM U 198, Route de Dole, 25000 Besancon, France

ABSTRACT identical to arylsulfatase C (7, 12). In mammalian tissues, the question remains whether the hydrolysis of E^S and DHEA-S is The activity of the two membrane-bound sulfatases, estrone catalyzed by a single or by 2 distinct membrane-bound enzymes and dehydroepiandrosterone sulfatases, are reported in human (10-12, 20). However, Dao ef al. (6) reported that, when human breast carcinoma tissues. In 21 tested tumors (12 from post- breast tumors exhibited estrone sulfatase activity, this enzyme menopausal women and 9 from nonmenopausal women), the was not consistently associated with DHEA sulfatase. two sulfatases were consistently present. The apparent Km val In this study, human breast cancers were investigated in order ues for estrone and dehydroepiandrosterone sulfatases were, to relate membrane-bound sulfatase activities to the hormonal respectively, 6.8 and 14.9 /Â¿M. status of the donors and to the hormone responsiveness of the In terms of maximal velocity, the sulfatase activities are not tumors as determined by estrogen and progesterone cytosol correlated to the estrogen or progesterone receptor status of receptors. The levels of plasma estrone-sulfate, the substrate of the tumors or to the hormonal status of the donors. It may be estrone sulfatase, were also determined in postmenopausal concluded that these two activities are not hormone dependent. women with or without breast cancer. Estrone sulfate, the substrate of estrone sulfatase, has been measured in plasma of postmenopausal women. The mean levels MATERIALS AND METHODS (nmol/liter) of plasma estrone sulfate were compared in post menopausal women with (n = 51) or without (n = 39) breast Chemicals cancer. For the first age group (48 to 55 years old), no statistically DHEA, estrone, cortisol, diethylstilbestrol, E,-S, and DHEA-S were purchased from Sigma Chemical Co. (St. Louis, MO.). R-5020 (17,21- significant difference in these levels was observed [1.91 Â±1.06 dimethyl-19-nor-4,9-pregnandiene-3,20-dione) was a generous gift from versus 1.50 Â±1.04 (mean Â±f0.95â€”;8 S.E.)]. . For the two other Roussel Uclaf (Paris, France). [17-a-mefhy/-3H]R-5020 (specific activity, -Jn 87 Ci/mmol), [6,7-3H] E,-S (specific activity, 53.0 Ci/mmol), [7-3H]DHEA- S (specific activity, 24.0 Ci/mmol), and [14C]DHEA (specific activity, 57.8 age groups (56 to 65 and 66 to 80 years of age), the differences were statistically significant [1.46 Â±0.43 versus 0.77 Â±0.21 (p mCi/mmol) were purchased from New England Nuclear (Boston, Mass.). [4-14C]estrone (specific activity, 52.0 mCi/mmol) was purchased from < 0.02) and 1.77 Â±0.53 versus 0.81 Â±0.22 (p < 0.01)]. The usefulness of plasma estrone 3-sulfate levels as an indi the Radio Chemical Centre (Amersham, England). Before use, steroids were purified as described previously (5, 20). TED buffer contained 10 cator of the real estrogen status of postmenopausal women is RIM Tris-HCI, pH 7.40, containing 1.5 mw Na2 EDTA and 0.5 rriM discussed. dithiothreitol. All reagents were of analytical grade (Merck, E. Merck, Darmstadt, Chelles, France). INTRODUCTION Tumor Tissue Preparation High concentrations of E^S3 (9, 15, 21, 22) in blood provide a potentially high flux of free estrogens to mammary tumors, due Human primary tumor specimens removed at the time of surgery were to the presence of arylsulfatase C (arylsulfate sulfohydrolase; promptly trimmed of fat and connective tissues and frozen in liquid EC 3.1.6.1) (6, 13, 31). The transformation of E,-S into 170- nitrogen. In all cases, histological diagnosis of carcinoma was confirmed from block sections. Tissues were processed within 2 weeks of storage. estradiol in human mammary carcinoma has been reported by The specimens, weighing 300 to 500 mg, were pulverized from the Wilking ef al. (31), and Vignon ef al. (30) concluded that estrogen supercooled state (Thermovac, Touzart et Matignon, Vitry sur Seine, sulfates can act in vitro as estrogen precursors in human breast France) and homogenized with a Potter-Elvehjem instrument with 6 cancer cells containing sulfatases. The biological role of Ei-S as volumes (w/v) of TED buffer. The homogenate was centrifugea at an estrogen precursor has also been found in other mammalian 105,000 x g for 1 hr. The supernatant (cytosol) was used for receptor tissues (5, 16, 24). assays. The pellet was suspended in an equal volume of 50 HIM Tris- The first step for the activation of Ei-S into the physiologically HCI, pH 7.0, containing 0.25 M saccharose and centrifuged at 1000 x g active 17ÃŸ-estradiol and estrone (5, 20, 24) is its hydrolysis by for 10 min. This supernatant (enzyme preparation) was used for DHEA sulfatases. Estrone sulfatase Â¡samembrane-bound enzyme (20, and estrone sulfatase activities. 29) and, in rat liver, it has been reported that this enzyme is PGR and ER Assays 1Supported by a grant from "UniversitÃ©de Franche-ComtÃ©," BesanÃ§on, and from "Etablissement Public RÃ©gionalde Franche-ComtÃ©," France. A single saturation assay was used according to the method of PichÃ³n 2To whom requests for reprints should be addressed. and Milgrom (18). Each assay was done in triplicate. 3The abbreviations used are: E,-S, estrone 3-sulfate; DHEA-S, dehydroepian PGR. Briefly, cytosol (100 p\) was added to a test tube containing 20 drosterone 3-sulfate; DHEA, dehydroepiandrosterone; PGR, cytosolic progester nw [3H]R-5020 and 10 MMof cortisol. Parallel tubes also contained 2 ^M one receptor; ER, cytosolic estrogen receptor; RIA, radioimmunoassay; FSH, of R-5020. After incubation for 2 hr at 4Â°,100 ÃŸ\of TED buffer, 40 miui follitropin. Received April 26,1983; accepted October 7,1983. Na2MoO4 glycerol 60% (v/v) were added. After 2 hr at 4Â°,200 ÃŸ\ofTED

FEBRUARY 1984 661

buffer, 20 mw Na2MoO4 glycerol 30% (v/v), 0.5% Norit A, and 0.05% Blood was collected in breast cancer patients just before mas dextran T-70 (Pharmacia, Bois d'Arcy, France) were added. After 30 min tectomy. Postmenopausal women without breast cancer were at 4Â°, the tubes were centrifugea, and an aliquot was removed for apparently healthy. Patients were grouped in 3 age groups. counting. These groups were chosen so that the mean ages for each of ER. The same protocol was used as for PGR with the following differences. The cytosol (100 ^l) was incubated with 10 nM [3H]17/3- them are not significantly different for women with and without estradiol with or without 100-fold excess of unlabeled diethylstilbestrol. breast cancer. No significant difference was noted for plasma After 18 hr at 4Â°,100 ii\ of TED buffer and 200 /Â¿IofTED buffer, 0.5% 170-estradiol or progesterone levels between the different Norit A, and 0.05% dextran were added and, after 3 hr at 4Â°,the tubes groups. E,-S was higher in postmenopausal women with breast were centrifugea, and an aliquot was removed for counting. cancer than in normal postmenopausal women. The differences Specific binding was considered to be the difference between total were statistically significant only for the groups 56 to 65 and 66 and nonsaturable binding (statistical analysis of differences was calcu to 80 years of age. Previously, some of us did not notice such lated using Student's t test). Tumors with receptor values below 10 fmol/ an increase of E,-S in postmenopausal women with breast mg cytosol protein were considered as clinically receptor poor (PGR~ and ER-). cancer. However, the results had not been compared by age group. Although statistically nonsignificant, the higher levels of E!-S found in women without breast cancer who were 48 to 55 Estrone and DHEA Sulfatase Assays years old can explain this difference (21). Factors such as the subject's weight or degree of obesity influence the plasma Ei-S The method has been described previously (20). Briefly, assays were carried out at 5 substrate concentrations of 2, 3, 5, 10, and 20 nu in concentrations in postmenopausal women (15). However, in the 0.05 M Tris-HCI buffer, pH 7.3, for DHEA sulfatase or 1, 2, 3, 5, and 10 present study, no statistical difference was observed in weight Â¿IMin 0.05 M Tris-HCI buffer, pH 7.0, for estrone sulfatase in a final (p > 0.10) between postmenopausal women with or without volume, including enzyme preparation, of 0.5 ml. The reaction was started by adding the enzyme preparation and stopped after 1 hr at 37Â° breast cancer. Steroid Sulfatase Activities. Estrone and DHEA sulfatase by adding 1 ml of 0.1 M Na2CO3. Liberated DHEA or estrone was activities were measured in breast carcinoma tissues. Tumors extracted by 4 ml of petroleum benzin or diethyl ether, respectively, and the methodological losses were corrected by [14C]DHEA or [14C]estrone. were obtained from 12 postmenopausal women (age, 63.2 Â±9.0 The method was optimized Â¡nterms of incubation time, quantity of years; plasma FSH, 35.13 Â±12.47 ID/liter; mean Â±f0.95â€”) and enzyme preparation, and concentrations in substrates for breast cancers. \/n Lineweaver-Burk reciprocal plots were drawn (lines were calculated by from 9 nonmenopausal women (age, 41.9 Â±4.8; plasma FSH, the method of least mean squares) to determine Kmand V,â„¢Â». 5.49 Â±2.66). E, and DHEA sulfatase activities were consistently Hormone Assays present in all tested tumors. A typical Lineweaver-Burk reciprocal plot is presented (Chart 1). This plot was chosen in order to give Blood samples were collected on EDTA by venipuncture between 8 an example of steroid sulfatase inhibition by high substrate and 10 a.m. from subjects who had fasted for 12 hr. Plasma was stored at -20Â° in several assay-tubes until processing. Commercial RIA kits concentration. Such an inhibition is usual for steroid sulfatase activities (see review in Ref. 20). The Km and Vâ„¢,,values are purchased from BioMÃ©rieux (Lyon, France) were used for the determi nation of plasma 17/i-estradiol, progesterone, and FSH according to the reported in Table 2 according to the hormonal status of the manufacturer's procedure as reported previously (20, 21). Ei-S in plasma donors. No statistically significant difference was observed be was measured by a specific method developed in our laboratory (21). tween the 2 groups, i.e., menopausal and nonmenopausal Briefly, free steroids were extracted from plasma with diethyl ether, and women. It appears that the kinetic parameters of estrone and Ei-S was isolated with use of Vlitos' reagent (mÃ©thylÃ¨neblue in diluted DHEA sulfatases are not influenced by the hormonal status of H2SO4/Na2SO4 solution). After enzyme hydrolysis, free estrone was the donors. The mean value of Km is lower for estrone sulfatase isolated by Celite chromatography and measured by RIA (Estrone RIA (6.75 fiM) than for DHEA sulfatase (14.89 U.M;n = 21). The kit; BioMÃ©rieux).The precision was 10%. activity of estrone sulfatase was consistently higher than that of DHEA sulfatase, and the 2 activities were correlated in all tested RESULTS tumors (r - 0.72; p = 0.001). For postmenopausal women, no statistically significant correlation was found between age and Hormonal Status.The hormonal status of postmenopausal estrone or DHEA sulfatase activities (p = 0.93 and p = 0.55). women (FSH: 48.8 Â±6.1 Ill/liter; mean Â±f095â€”) with (n = 51) Estrone and DHEA sulfatase activities were correlated with the presence or the absence of ER or PGR receptors (Chart 2). The or without (n = 39) breast cancer, was compared (Table 1). receptor distributions, in percentage of the total tested tumors

Table 1 Plasma hormones of postmenopausal women with or without breast cancer Classes(yr)48-5556-6566-80Status (n)Without (yr)51 (nmol/liter)1. (pmol/liter)90 (nmol/liter)1. .3 Â±2.9a51.4 "1.9150 Â±1.04a Â±46a152 24 Â±0.82a2.25 (6)With breast cancer inc<0 (9)Withoutbreast cancer Â±1.859.5 Â±1.060.77 Â±12288 Â±1.191 Â±0.211.46 Â±2573 .78 Â±0.701 3)With breast cancer (1 Â±1.860.2 02^n (17)Withoutbreast cancer Â±1.173.1 Â±0.430.81 Â±16109 .79 Â±0.481.83 (20)Withbreast cancer Â±2.072.6 Â±0.221 niEstradici Â±2382 Â±0.412.1 breast cancer (25)Age Â±1.8Estrone-sulfate.77 Â±0.53P^>n Â± 23PMÂ«5Ã–NSMCProgesterone6 Â±0.75PMOMOMC

"Mean Â±i09s-p. \n " Mean of duplicate determinations. c Values were compared statistically by Mann-Whitney U test. a NS, not significant.

662 CANCER RESEARCH VOL. 44

(n = 21), were ER+PGFT, 55.0%; ER+PGFT, 20.0%; EFTPGR+, S. Using a histochemical method, Koudstaal (13) showed aryl- 10.0%; and ER~PGR~, 15.0%. (The small number of cases has sulfatase activity in only 14 of the 83 breast carcinomas studied. prevented us from making a distinction between menopausa! The activities, reported in terms of pmol product/mg protein/min and nonmenopausal women.) No significant difference between in the relevant literature, were lower than those reported here the presence and the absence of receptors was found in the [(mean, 0.414 Â±0.071; n = 27) for estrone sulfatase activity by activities of estrone sulfatase or DHEA sulfatase. Wilking ef al. (31) and 0.297 Â±0.095 (n = 16) and 0.015 Â±0.05 (n = 9) for estrone and DHEA sulfatase activities by Dao ef al. (6)]. In agreement with the latter authors, the levels of DHEA DISCUSSION sulfatase activity have been consistently found to be lower than The isotope dilution method used to study estrone and DHEA those of estrone sulfatase. The Km values reported here are sulfatase activities was the preferred method so as to be able widely dispersed. An endogenous factor may be responsible for to: (a) evaluate 2 kinetic parameters, Vmaxand Km;and (b) obtain the variation of the Kmfrom tumor to tumor. In sheep brain, such the highest possible sensitivity to detect low amount of enzyme. an endogenous factor decreasing arylsulfatase C Km has been reported (14). However, the mean Km values found for estrone Published procedures (6, 31) determine sulfatase activities at and DHEA sulfatases are in the same order of magnitude (10~6 one level of substrate. The measured velocities may be de creased by the presence and concentration of endogenous M) as those reported in different human tissues (11, 20, 27). steroids used as substrates or endogenous inhibitors. Using 5 Estrone and DHEA sulfatase activities are present in all tested different concentrations of substrate, we could express enzyme human breast tumors regardless of their ER or PGR status. activities in terms of Vmax.This kinetic parameter is independent Moreover, these 2 activities are not correlated to the hormonal of substrate concentration and remains unchanged in the pres status of the donors. Adams ef al. (3), Pewnim ef al. (17), and ence of endogenous competitive inhibitors. These reasons ex Wilking ef al. (31) reported a correlation between steroid receptor plain why there were consistently estrone and DHEA sulfatase status and estrogen sulfotransferase or 17/i-hydroxysteroid de- activities in breast carcinoma tissues. Dao ef al, (6) tested 85 tumor preparations; 31 tumors exhibited estrone sulfatase activ E, sulfatÃ³se DHEA sulfatase ity, and 19 tumors also exhibited sulfatase activity toward DHEA- 200 80

pmol Ej.min'^mg protein'1

150 60

t 100 40

50 20

-M- ER' EU* ER' PGR' PGR- PGR' POR" 10 uM Chart 2. Correlation between estrone and DHEA sulfatase activities and the presence or the absence of ER or PGR. Estrone (E,) sulfatase (A) and DHEA Chart 1. Relationship between estrone production (pmol/min/mg protein) from sulfatase (A) in menopausal women. Estrone sulfatase (â€¢)andDHEA sulfatase (O) different concentrations of E,-S. The Lineweaver-Burk plot is given (inset). in nonmenopausal women.

Table 2 Â£1and DHEA sulfatase activities in breast carcinoma tissues sulfatase9Kâ€ž sulfatase"Vâ„¢,

(pmol DHEA/mg/ donorMenopausalStatus of the protein/min)7.38(/IM) Vâ„¢,(pmol E^rng protein/min)16.30(1.40-63.10)Kâ€ž(fiM) womenEstrone (1.70-30.30) 61 .24 (5.80-1 68)DHEA 21.22(1.30-79)

Nonmenopausal women 5.91 (0.91-13.60) 56.43(3.47-166) 13.02(1.40-28.00) 16.69(1.80-39)

P" >0.10 >0.10 >0.10 >0.10 a Mean (extreme values). " Statistically compared by Mann-Whitney U test.

FEBRUARY 1984 663

hydrogenase activities in human mammary cancer. This differ 345, 1972. 8. Eckert, R. L., and Katzenellenbogen, B. S. Human endometrial cells in primary ence may be explained only if we suppose that, in breast cancers tissue culture: modulation of the progesterone receptor level by natural and as in human endometrium (28, 29), these 2 enzymes are induced synthetic estrogens in vitro. J. Clin. Endocrinol. Metab., 52: 699-708,1981. by progestogen, whereas estrone and DHEA sulfatases are not 9. Franz, C., Watson, D., and Longcope, C. Estrone sulfate and dehydroepian drosterone sulfate concentrations in normal subjects and men with cirrhosis. hormone dependent. DHEA-S as well as Ei-S may be sources Steroids, 34: 563-573, 1979. of estrogen, since free DHEA liberated from DHEA-S may be 10. French, A. P., and Warren, J. C. Properties of steroid sulphatase and arylsul phatase activities of human placenta. Biochem. J., 705: 233-241,1967. converted into estrogens in many human breast tumors (1, 4). 11. Gauthier, R., Vigneault, N., Bleau, G., Chapdelaine, A., and Roberts, K. D. 5-Androstene-3!0,17j3-diol, another product of DHEA, has been Solubilization and partial purification of steroid sulfatase of human placenta. implicated as having a possible, influential estrogen action in Steroids, 37: 783-798, 1978. hormone-responsive breast cancer (2). The local metabolism of 12. Iwamori, M., Moser, H. W., and Kishimoto, Y. Solubilization and partial purifi cation of steroid sulfatase from rat liver: characterization of estrone sulfatase. steroid hormones may be taken into account to evaluate the Arch. Biochem. Biophys., 774. 199-208, 1976. 13. Koudstaal, J. The histochemical demonstration of arylsulphatase in human hormonal status of human breast cancer. The intracellular levels tumours. Eur. J. Cancer, 77: 809-813,1975. of estrone and DHEA liberated from their sulfoconjugated pre 14. Lakshmi, S., and Balasubramanian, A. S. Studies on the chaotropically solu- cursors depend on the estrone and DHEA sulfatase activities bilized arylsulfatase C and estrone sulfatase of sheep brain. Biochim. Biophys. Acta, 567: 184-195,1979. and the circulating hormone concentrations. A significant in 15. Noel, C. T., Reed, M. J., Jacobs, H. S., and James, V. H. T. The plasma crease of plasma E^S has been found in postmenopausal concentration of destrone sulphate in postmenopausal women: lack of diurnal women with breast cancer. Studies in the plasma levels of variation, effect of ovariectomy, age and weight. J. Steroid Biochem., 74: 1101-1105,1981. unconjugated estrogens in breast cancer patients have been 16. Payne, A. H., Lawrence, C.C., Foster, D. L., and Jaffe, R. B. Intranuclear largely inconclusive (see review in Refs. 19 and 23). Samojlik ef binding of 17/J-estradiol and estrone in female ovine pituitaries following a/. (25) have recently supported the usefulness of plasma E,-S incubation with estrone sulfate. J. Biol. Chem., 248: 1598-1602,1973. 17. Pewnim, T., Adams, J. B., and Ho, K. P. A relationship between estrogen determinations to measure the real estrogen status of postmen sulfurylation and estrogen and progesterone receptor status in human mam opausal women, since Ei-S levels are approximately 10-fold mary carcinoma. Cancer Res., 40: 1360-1362,1980. 18. PichÃ³n, M. F., and Milgrom, E. Characterization and assay of progesterone higher than unconjugated estrogens (21,26). In postmenopausal receptor in human mammary carcinoma. Cancer Res., 37: 464-471,1977. women, an emerging concept of stimulation of estrogen-respon 19. Poortman, J. Breast Cancer: hormonal factors in its development. In: B. A. sive breast cancers can be formulated. Estrone sulfatase regu Stoll (ed.). Hormonal Management of Endocrine-related Cancer, pp. 51-63. lated the transport of E,-S from the plasma to the cell tumors as 20. Prost, O., and Adessi, G. L. Estrone and dehydroepiandrosterone sulfatase activities in normal and pathological human endometrium biopsies. J. Clin. unconjugated estrone. The biological activity of estrone in hor Endocrinol. Metab., 56: 653-661, 1983. mone-responsive tissues has been reported by Vignon ef al. (30) 21. RÃ©my-Martin,A., Prost, O., Nicollier, M., Burnod, J., and Adessi, G. L. Estrone Sulfate concentrations in plasma of normal individuals, postmenopausal women in human breast cancer cells and by Eckert and Katzenellenbo- with breast cancer and men with cirrhosis. Clin. Chem., 29: 86-89,1983. gen (8) in human endometrial cells. 22. Roberts, K. D., Rochefort, J. G., Bleau, G., and Chapdelaine, A. Plasma estrone sulfate levels in postmenopausal women. Steroids, 35:179-187,1980. 23. Rose, D. P. Endogeneous hormones in the etiology and clinical course of breast cancer. In: D. P. Rose (ed.), Endocrinology of Cancer, Vol. 1, pp. 22- 52. Boca Raton, Fla.: CRC Press Inc., 1979. REFERENCES 24. Rossier, G., and Pierrepoint, C. G. Oestrogen metabolism in sheep myomet- 1. Abul-Haji, Y. J. Metabolism of dehydroepiandrosterone by hormone dependent rium. J. Reprod. FÃ©rtil.,37: 43-49, 1974. and hormone independent human breast carcinoma. Steroids. 26: 488-500 25. Samojlik, E., Santen, R. J., and Worgul, T. J. Plasma estrone-sulfate assess 1975. ment of reduced estrogen production during treatment of metastatic breast 2. Adams, J. B., Archibald, L., and Seymour-Munn, K. Dehydroepiandrosterone carcinoma. Steroids, 39: 497-507, 1982. and androst-5-ene-3ÃÂ¡,17fÂ¡-diolinhuman mammary cancer cytosolic and nu 26. Stoa, K. F., and Myking, O. L. Destrone sulphate. A major circulating oestro clear compartments and their relationship to estrogen receptor. Cancer Res gen. In: K. Fotherby, and S. B. Pal (eds.), Hormones in Normal and Abnormal 40:3815-3820,1980. Human Tissues, pp. 541-571. New York: Walter de Gruyter, Inc., 1981. 3. Adams, J. B., Pewnim, T., Chandra, D. P., Archibald, L., and Foo, M. S. A 27. Townsley, J. D. Further studies on the regulation of human placental steroid correlation between estrogen sulfotransferase levels and estrogen receptor 3-sulfatase activity. Endocrinology, 93: 172-181, 1973. status in human primary breast carcinoma. Cancer Res., 39: 5124-5126, 28. Tseng, L., and Liu, H. C. Stimulation of arylsulfotransferase activity by proges- 1979. tins in human endometrium in vitro. J. Clin. Endocrinol. Metab., 53: 418-421, 4. Adams, J. B., and Wong, M. S. F. Paraendocrine behavior of human breast 1981. carcinoma: in vitro transformation of steroids to physiologically active hor 29. Tseng, L., and Mazella, J. Cyclic change of estradiol metabolic enzymes in mones. J. Endocrinol., 41: 41-52, 1968. human endometrium during the menstrual cycle. In: F. A. Kimball (ed.), The 5. Adessi, G. L.. Nhuan, T. Q., and Vingler, P. In vivo and in vitro metabolism of Endometrium, pp. 211-225. Jamaica, New York: Spectrum Publications, Inc., estrone and estradiol-17(Ã and their 3-sulfates in pregnant female guinea-pigs: 1980. a plausible prehormone role of estrogen-sulfates in the maternal uterus. J. 30. Vignon. F., Terqui, M., Westley, B., Derocq, D., and Rochefort, H. Effects of Steroid Biochem., 76: 107-116, 1982. plasma estrogen sulfates in mammary cancer cells. Endocrinology, 706:1079- 6. Dao, T. L., Hayes, C., and Libby, P. R. Steroid sulfatase activities in human 1086, 1980. breast tumors (38109). Proc. Soc. Exp. Biol. Med., 746: 381-384,1974. 31. Wilking. N., CaristrÃ¶m, K., Gustafsson, S. A., Skoldefors, H., and Tollbone, O. 7. Dolly, J. O., Dodgson, K. S., and Rose, F. A. Studies of the oestrogen Oestrogen receptors and metabolism of oestrone sulphate in human mammary sulphatase and arylsulphatase C activities of rat liver. Biochem. J., 728: 337- carcinoma. Eur. J. Cancer, 76: 1339-1344,1980.

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Odile Prost, Marie O. Turrel, Nicole Dahan, et al.

Cancer Res 1984;44:661-664.

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