Journal of Clinical Endocrinology & Metabolism, Vol 59, 29-33, Copyright © 1984 by Endocrine Society

ARTICLES

In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway

SJ Santner, PD Feil and RJ Santen

Estrone and estradiol concentrations in breast tumor tissue are an order of magnitude higher than circulating plasma levels in postmenopausal women with breast cancer. Local production of estrogen in the neoplastic tissue is one of several possible explanations for this plasma/tissue gradient. This study evaluated breast tumor estrogen production via the estrone sulfate to estrone (sulfatase) pathway and compared this with the androstenedione to estrone (aromatase) system in human and rodent mammary tumors. Estrogen production from estrone sulfate was related linearly with time and tissue concentrations, exhibited an apparent Km of 20 microM, and produced a linear Eadie- Hofstee kinetic plot consistent with a single class of enzymatic sites. Measurement of sulfatase in 35 human breast tumors using enzyme saturating conditions revealed estrone production ranging from 0.8-125 mumol/g protein . h. The corresponding range in host mammary tumors was 3.5-7.1 mumol/g protein . h. In human breast tumors, sulfatase activity did not correlate with the levels of estrogen receptor or progesterone receptor. Comparison of sulfatase with aromatase activity in human tumors at physiological levels of substrate revealed estrone formation via sulfatase of 2.8 pmol estrone produced/g protein . h, while aromatase produced only 0.27 pmol/g protein . h. In rat mammary tumors, sulfatase activity was similar to that in human tumors, whereas aromatase activity could not be detected, even with a highly sensitive assay. Thus, estrone sulfatase appears to be the enzyme primarily responsible for intratissue estrone production in hormone-dependent breast carcinomas.

This article has been cited by other articles:

				A. Purohit, L. Fusi, J. Brosens, L.W.L. Woo, B.V.L. Potter, and M.J. Reed Inhibition of steroid sulphatase activity in endometriotic implants by 667 COUMATE: a potential new therapy Hum. Reprod., February 1, 2008; 23(2): 290 - 297. [Abstract] [Full Text] [PDF]

				S. J. Stanway, A. Purohit, L.W. L. Woo, S. Sufi, D. Vigushin, R. Ward, R. H. Wilson, F. Z. Stanczyk, N. Dobbs, E. Kulinskaya, et al. Phase I Study of STX 64 (667 Coumate) in Breast Cancer Patients: The First Study of a Steroid Sulfatase Inhibitor Clin. Cancer Res., March 1, 2006; 12(5): 1585 - 1592. [Abstract] [Full Text] [PDF]

				N. Honma, K. Takubo, M. Sawabe, T. Arai, F. Akiyama, G. Sakamoto, T. Utsumi, N. Yoshimura, and N. Harada Estrogen-Metabolizing Enzymes in Breast Cancers from Women over the Age of 80 Years J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 607 - 613. [Abstract] [Full Text] [PDF]

				T. Suzuki, Y. Miki, Y. Nakamura, T. Moriya, K. Ito, N. Ohuchi, and H. Sasano Sex steroid-producing enzymes in human breast cancer Endocr. Relat. Cancer, December 1, 2005; 12(4): 701 - 720. [Abstract] [Full Text] [PDF]

				M. J. Reed, A. Purohit, L. W. L. Woo, S. P. Newman, and B. V. L. Potter Steroid Sulfatase: Molecular Biology, Regulation, and Inhibition Endocr. Rev., April 1, 2005; 26(2): 171 - 202. [Abstract] [Full Text] [PDF]

				T. Walle, F. Hsieh, M. H. DeLegge, J. E. Oatis Jr., and U. K. Walle HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS Drug Metab. Dispos., December 1, 2004; 32(12): 1377 - 1382. [Abstract] [Full Text] [PDF]

				H. Utsunomiya, K. Ito, T. Suzuki, T. Kitamura, C. Kaneko, T. Nakata, H. Niikura, K. Okamura, N. Yaegashi, and H. Sasano Steroid Sulfatase and Estrogen Sulfotransferase in Human Endometrial Carcinoma Clin. Cancer Res., September 1, 2004; 10(17): 5850 - 5856. [Abstract] [Full Text] [PDF]

				L. C. Ciobanu, V. Luu-The, C. Martel, F. Labrie, and D. Poirier Inhibition of Estrone Sulfate-induced Uterine Growth by Potent Nonestrogenic Steroidal Inhibitors of Steroid Sulfatase Cancer Res., October 1, 2003; 63(19): 6442 - 6446. [Abstract] [Full Text] [PDF]

				T. Suzuki, T. Nakata, Y. Miki, C. Kaneko, T. Moriya, T. Ishida, S. Akinaga, H. Hirakawa, M. Kimura, and H. Sasano Estrogen Sulfotransferase and Steroid Sulfatase in Human Breast Carcinoma Cancer Res., June 1, 2003; 63(11): 2762 - 2770. [Abstract] [Full Text] [PDF]

				F. FAUCHER, L. LACOSTE, and V. LUU-THE Human Type 1 Estrogen Sulfotransferase: Catecholestrogen Metabolism and Potential Involvement in Cancer Promotion Ann. N.Y. Acad. Sci., June 1, 2002; 963(1): 221 - 228. [Abstract] [Full Text] [PDF]

				J. Geisler, S. Detre, H. Berntsen, L. Ottestad, B. Lindtjørn, M. Dowsett, and P. E. Lønning Influence of Neoadjuvant Anastrozole (Arimidex) on Intratumoral Estrogen Levels and Proliferation Markers in Patients with Locally Advanced Breast Cancer Clin. Cancer Res., May 1, 2001; 7(5): 1230 - 1236. [Abstract] [Full Text]

				M. R. James, T. C. Skaar, R. Y. Lee, A. MacPherson, J. A. Zwiebel, B. S. Ahluwalia, F. Ampy, and R. Clarke Constitutive Expression of the Steroid Sulfatase Gene Supports the Growth of MCF-7 Human Breast Cancer Cells in Vitro and in Vivo Endocrinology, April 1, 2001; 142(4): 1497 - 1505. [Abstract] [Full Text]

				X. Xu, A. M. Duncan, K. E. Wangen, and M. S. Kurzer Soy Consumption Alters Endogenous Estrogen Metabolism in Postmenopausal Women Cancer Epidemiol. Biomarkers Prev., August 1, 2000; 9(8): 781 - 786. [Abstract] [Full Text]

				H. Erbas and L. C Lai Effect of transforming growth factor {beta}2 on oestrogen metabolism in the MCF-7 breast cancer cell line J. Clin. Pathol., April 1, 2000; 53(4): 322 - 324. [Abstract] [Full Text] [PDF]

				R. M. Harris, R. H. Waring, C. J. Kirk, and P. J. Hughes Sulfation of "Estrogenic" Alkylphenols and 17beta -Estradiol by Human Platelet Phenol Sulfotransferases J. Biol. Chem., January 7, 2000; 275(1): 159 - 166. [Abstract] [Full Text] [PDF]

				T. Utsumi, N. Yoshimura, S. Takeuchi, J. Ando, M. Maruta, K. Maeda, and N. Harada Steroid Sulfatase Expression Is an Independent Predictor of Recurrence in Human Breast Cancer Cancer Res., January 1, 1999; 59(2): 377 - 381. [Abstract] [Full Text] [PDF]

				M. J. Reed and A. Purohit Breast Cancer and the Role of Cytokines in Regulating Estrogen Synthesis: An Emerging Hypothesis Endocr. Rev., October 1, 1997; 18(5): 701 - 715. [Abstract] [Full Text]

				S. J. Santner, R. J. Pauley, L. Tait, J. Kaseta, and R. J. Santen Aromatase Activity and Expression in Breast Cancer and Benign Breast Tissue Stromal Cells J. Clin. Endocrinol. Metab., January 1, 1997; 82(1): 200 - 208. [Abstract] [Full Text] [PDF]