Comparison of estrogen concentrations, estrone sulfatase and aromatase activities in normal, and in cancerous, human breast tissues

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Abstract

In the present study, the concentrations of estrone (E1), estradiol (E2) and their sulfates (E1S and E2S), as well as the sulfatase and aromatase activities, were evaluated in post-menopausal patients with breast cancer. Comparative studies of the evaluation of these parameters were carried out in (a) tumor tissue, (b) areas surrounding the tumor, and (c) areas distant from the tumor (glandular tissue) which were considered as normal tissue. The levels (in pm/g; mean ± SEM) were: for E1 in the (a) area: 320±95; in (b): 232±86; and in (c): 203±71; for E2 in the (a) area: 388±106; in (b): 224±48; and in (c): 172±80; for E1S in the (a) area: 454±110; in (b): 259±90; and in (c): 237±65; for E2S in the (a) area:318±67; in (b): 261±72; and in (c): 232±75, respectively. The values of E1S and E2 were significantly higher in the tumor tissue than in the area considered as normal. In all the tissues studied, the sulfatase activity was much higher than aromatase (130–200). In addition, the sulfatase levels were significantly higher in the peripheral and in the tumor tissue than in the area considered as normal. The levels of aromatase were significantly higher in tumoral than in normal tissue. The present data extend the “intracrine concept” for breast cancer tumors. The physiopathology and clinical significance as promoter parameters in breast cancer is to be explored.

Introduction

There is substantial information that the human mammary cancer tissue contains the enzyme systems (aromatase, sulfatase, 17β-hydroxysteroid dehydrogenase) necessary for the last steps in the formation of estradiol (E2), the hormone that plays an important role in the origin and evolution of this disease [1], [2], [3]. Estrogens in this carcinoma tissue can originate through two main pathways, one from aromatase, which converts androgens to estrogens [4], [5], [6] and the other from sulfatase, which converts estrone sulfate into estrone (E1) [7], [8], [9], [10], [11], [12]. Estrone is converted to the biologically active estradiol by the action of the 17β-hydroxysteroid dehydrogenase (Type I) [13], [14], [15], [16]. Quantitative determinations in breast cancer tissues indicate that the “estrone sulfatase pathway” is 40–500 times that of the “aromatase pathway” [17], [18]. The present study compares the concentrations of E1, E2, and their sulfates (E1S and E2S), as well as the aromatase and estrone sulfatase activities in (i) breast cancer tissue, (ii) the peripheral area of the tissue, and (iii) the area of the mammary gland considered as normal, in patients with breast cancer.

Section snippets

Chemicals

[6,7-3H]-Estrone sulfate (SA: 49.0 Ci/mmol), [7-3H]-testosterone (SA: 27.7 Ci/mmol, [6,7-3H]-estrone (SA: 41.9 Ci/mmol), [4-14C]-estrone (SA: 57.6 mCi/mmol), [4-14C]-estradiol (SA: 57.0 mCi/mmol), were obtained from New England Nuclear Division (Du Pont de Nemours, Les Ulis, France). Estrone sulfate ammonium salt and β-NADPH were purchased from Sigma–Aldrich Chimie (St Quentin, Fallavier, France). Estrone and estradiol were obtained from Steraloids (Touzart et Matignon, Vitry-sur-Seine, France).

Estrogen concentrations in the different areas of the breast

Mammary tissues of post-menopausal patients with breast tumors were divided into three areas: tumoral, peripheral and normal tissue. Fig. 1 shows the levels of the most important free and conjugated estrogens: estrone (E1), estradiol (E2), estrone sulfate (E1S) and estradiol sulfate (E2S) in each of these three areas. It was observed that: (1) the concentrations of the four estrogens were higher in the tumoral tissue than in the peripheral tissue or the areas of the breast considered as normal;

Discussion

One of the important findings of the present data is the high concentration of various estrogens in the mammary gland of peri- and post-menopausal patients with breast cancer. This is of particular interest as during this period of life the ovary has ceased to produce these estrogens, suggesting that the hormone can be produced in the same organ where it exerts its biological response, which is also in agreement with the information that breast cancer tissue possesses all the enzymes necessary

Conclusion

The breast tumoral process is characterized by a modification of the estrogen metabolism, which corresponds to the establishment of two gradients: E1S and E2, and sulfatase and aromatase activities, when the tumoral and normal breast tissue are compared. These results indicate that therapeutical use of Selective Estrogen Enzyme Modulators (SEEM) can be an important additional treatment for breast cancer by reducing the rate of E2 in the tumor.

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