Abstract
Oestrone sulphatase may be an important means of production of intra-tumoural oestrogens in breast cancer cells. The N-nitrosomethylurea induced rat mammary tumours, which is a good model of human breast carcinoma, was utilised to examine the significance of intra-tumoural oestrone sulphatase levels. The particular fraction (100,000 g pellet) was prepared from both the liver and the tumour of NMU treated rats and assayed for sulphatase activity. The tumour enzyme had an optimum pH of 7.2, Km value of 14.8 microM and Vmax of 0.90 nmoles min-1 mg-1, while the hepatic enzyme was optimal at pH 7.4, Km of 10.8 microM and Vmax of 3.71 nmoles min-1 mg-1. The relationship of intra-tumoural sulphatase levels with tumour regression and progression in endocrine responsive tumours was investigated. Tumour regression as a result of oophorectomy was associated with a significantly decreased intra-tumoural sulphatase level (mean level = 0.165 nmoles min-1 mg-1) in comparison to a control group (mean level = 0.319 nmoles min-1 mg-1, P less than 0.05) in which the tumours remained stable. This significant difference was not observed in the corresponding hepatic samples suggesting that it is the intra-tumoural rather than the peripheral production of oestrogens by oestrone sulphatase that is important in supporting growth of endocrine responsive tumours.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Connolly P. B., Resko J. A. Estrone sulfatase activity in rat brain and pituitary: effects of gonadectomy and the estrous cycle. J Steroid Biochem. 1989 Nov;33(5):1013–1018. doi: 10.1016/0022-4731(89)90254-9. [DOI] [PubMed] [Google Scholar]
- Dolly J. O., Dodgson K. S., Rose F. A. Studies on the oestrogen sulphatase and arylsulphatase C activities of rat liver. Biochem J. 1972 Jun;128(2):337–345. doi: 10.1042/bj1280337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edery M., Goussard J., Dehennin L., Scholler R., Reiffsteck J., Drosdowsky M. A. Endogenous oestradiol-17beta concentration in breast tumours determined by mass fragmentography and by radioimmunoassay: relationship to receptor content. Eur J Cancer. 1981 Jan;17(1):115–120. doi: 10.1016/0014-2964(81)90220-6. [DOI] [PubMed] [Google Scholar]
- Eriksson L., Nilsson B., Carlström K., Oscarsson J., Eden S., von Schoultz B. Secretory pattern of growth hormone regulates steroid sulfatase activity in rat liver. J Steroid Biochem. 1989 Sep;33(3):413–416. doi: 10.1016/0022-4731(89)90331-2. [DOI] [PubMed] [Google Scholar]
- Fishman J., Nisselbaum J. S., Menendez-Botet C. J., Schwartz M. K. Estrone and estradiol content in human breast tumors: relationship to estradiol receptors. J Steroid Biochem. 1977 Aug;8(8):893–896. doi: 10.1016/0022-4731(77)90100-5. [DOI] [PubMed] [Google Scholar]
- Gullino P. M., Pettigrew H. M., Grantham F. H. N-nitrosomethylurea as mammary gland carcinogen in rats. J Natl Cancer Inst. 1975 Feb;54(2):401–414. [PubMed] [Google Scholar]
- Hartree E. F. Determination of protein: a modification of the Lowry method that gives a linear photometric response. Anal Biochem. 1972 Aug;48(2):422–427. doi: 10.1016/0003-2697(72)90094-2. [DOI] [PubMed] [Google Scholar]
- Henderson I. C., Canellos G. P. Cancer of the breast: the past decade (first of two parts). N Engl J Med. 1980 Jan 3;302(1):17–30. doi: 10.1056/NEJM198001033020104. [DOI] [PubMed] [Google Scholar]
- Kawano J., Kotani T., Umeki K., Oinuma T., Ohtaki S., Aikawa E. A monoclonal antibody to rat liver arylsulfatase C and its application in immunohistochemistry. J Histochem Cytochem. 1989 May;37(5):683–690. doi: 10.1177/37.5.2703703. [DOI] [PubMed] [Google Scholar]
- Loza M. C., Valencia A., Hicks J. J. Uterine estrogen sulfatase activity. Influence of steroid hormones and adenine nucleotides. J Steroid Biochem. 1990 Jul 4;36(4):301–303. doi: 10.1016/0022-4731(90)90221-d. [DOI] [PubMed] [Google Scholar]
- Millington D. S. Determination of hormonal steroid concentrations in biological extracts by high resolution mass fragmentography. J Steroid Biochem. 1975 Mar-Apr;6(3-4):239–245. doi: 10.1016/0022-4731(75)90139-9. [DOI] [PubMed] [Google Scholar]
- Naitoh K., Honjo H., Yamamoto T., Urabe M., Ogino Y., Yasumura T., Nambara T. Estrone sulfate and sulfatase activity in human breast cancer and endometrial cancer. J Steroid Biochem. 1989 Dec;33(6):1049–1054. doi: 10.1016/0022-4731(89)90408-1. [DOI] [PubMed] [Google Scholar]
- Prost O., Turrel M. O., Dahan N., Craveur C., Adessi G. L. Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. Cancer Res. 1984 Feb;44(2):661–664. [PubMed] [Google Scholar]
- Santner S. J., Feil P. D., Santen R. J. In situ estrogen production via the estrone sulfatase pathway in breast tumors: relative importance versus the aromatase pathway. J Clin Endocrinol Metab. 1984 Jul;59(1):29–33. doi: 10.1210/jcem-59-1-29. [DOI] [PubMed] [Google Scholar]
- Santner S. J., Leszczynski D., Wright C., Manni A., Feil P. D., Santen R. J. Estrone sulfate: a potential source of estradiol in human breast cancer tissues. Breast Cancer Res Treat. 1986;7(1):35–44. doi: 10.1007/BF01886734. [DOI] [PubMed] [Google Scholar]
- Santner S. J., Levin M. C., Santen R. J. Estrone sulfate stimulates growth of nitrosomethylurea-induced breast carcinoma in vivo in the rat. Int J Cancer. 1990 Jul 15;46(1):73–78. doi: 10.1002/ijc.2910460115. [DOI] [PubMed] [Google Scholar]
- Thijssen J. H., Blankenstein M. A. Endogenous oestrogens and androgens in normal and malignant endometrial and mammary tissues. Eur J Cancer Clin Oncol. 1989 Dec;25(12):1953–1959. doi: 10.1016/0277-5379(89)90377-5. [DOI] [PubMed] [Google Scholar]
- Thorsen T., Tangen M., Støa K. F. Concentration of endogenous oestradiol as related to oestradiol receptor sites in breast tumor cytosol. Eur J Cancer Clin Oncol. 1982 Apr;18(4):333–337. doi: 10.1016/0277-5379(82)90002-5. [DOI] [PubMed] [Google Scholar]
- Urabe M., Yamamoto T., Naitoh K., Honjo H., Okada H. Estrone sulfatase activity in normal and neoplastic endometrial tissues of human uterus. Asia Oceania J Obstet Gynaecol. 1989 Mar;15(1):101–106. doi: 10.1111/j.1447-0756.1989.tb00160.x. [DOI] [PubMed] [Google Scholar]
- Wilkinson J. R., Williams J. C., Singh D., Goss P. E., Easton D., Coombes R. C. Response of nitrosomethylurea-induced rat mammary tumor to endocrine therapy and comparison with clinical response. Cancer Res. 1986 Sep;46(9):4862–4865. [PubMed] [Google Scholar]
- Williams J. C., Gusterson B., Humphreys J., Monaghan P., Coombes R. C., Rudland P., Neville A. M. N-methyl-N-nitrosourea-induced rat mammary tumors. Hormone responsiveness but lack of spontaneous metastasis. J Natl Cancer Inst. 1981 Jan;66(1):147–155. [PubMed] [Google Scholar]
- van Landeghem A. A., Poortman J., Nabuurs M., Thijssen J. H. Endogenous concentration and subcellular distribution of estrogens in normal and malignant human breast tissue. Cancer Res. 1985 Jun;45(6):2900–2906. [PubMed] [Google Scholar]
