Concentration of endogenous oestradiol as related to oestradiol receptor sites in breast tumor cytosol

Thorsen, T.; Tangen, M; Støa, K. F.

doi:10.1016/0277-5379(82)90002-5

Cited by 55 publications

(21 citation statements)

References 21 publications

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“…After menopause, serum estradiol (E2) levels decrease to be as low as about 1/10 of that of premenopausal women. 3,4 However, it has been reported that, even after menopause, intratumoral E2 levels are maintained at high levels that are equivalent to those in premenopausal women. 4 High intratumoral E2 levels in postmenopausal women are supposed to be maintained by the intratumoral biosynthesis of estrogens.…”

Section: Abstract: Breast Cancer; Estrogens; Aromatase; Sulfatase; 1mentioning

confidence: 99%

Involvement of up-regulation of 17?-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers

et al. 2001

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Estradiol (E2) and estrone (E1) levels as well as mRNA expression levels of aromatase, sulfatase and 17␤-hydroxysteroid dehydrogenase type 1 (17␤-HSD1) in breast cancer tissues were studied to elucidate the mechanism involved in the maintenance of the intratumoral high E2 levels in postmenopausal patients with very low serum E2 levels. Intratumoral E2 levels of postmenopausal patients (127.2 ؎ 17.5 pg/g) (mean ؎ SE) were not significantly different from those of premenopausal patients (110.1 ؎ 10.1 pg/g) (p ‫؍‬ 0.36). The mRNA expression levels of aromatase and sulfatase, determined by a quantitative real-time PCR, were not significantly different between premenopausal and postmenopausal breast cancers, but 17␤-HSD1 mRNA expression levels were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.05). Intratumoral E2/E1 ratios were significantly higher in postmenopausal than premenopausal breast cancers (p < 0.01). These results demonstrate that the increased conversion from E1 to E2 catalyzed by 17␤-HSD1 may play an important role in the maintenance of the intratumoral high E2 levels in postmenopausal patients. © 2001 Wiley-Liss, Inc. Key words: breast cancer; estrogens; aromatase; sulfatase; 17␤-HSD1It has been shown that estrogens play an important role in the growth of hormone-dependent breast cancers. 1,2 In premenopausal women, the major source of estrogens is the ovary, and estrogens produced in the ovary are taken up by tumors and stimulate tumor growth. After menopause, serum estradiol (E2) levels decrease to be as low as about 1/10 of that of premenopausal women. 3,4 However, it has been reported that, even after menopause, intratumoral E2 levels are maintained at high levels that are equivalent to those in premenopausal women. 4 High intratumoral E2 levels in postmenopausal women are supposed to be maintained by the intratumoral biosynthesis of estrogens. [5][6][7] E2 is synthesized in breast cancer tissues through 2 pathways (aromatase and sulfatase pathways). 8 -10 In the aromatase pathway, androstenedione taken up by the tumor from the blood is aromatized into estrone (E1) and then catalyzed into E2 by 17-␤hydrox-ysteroid dehydrogenase type 1 (17-␤ HSD1). [11][12][13] In the sulfatase pathway, estrone sulfate (E1S) taken up by the tumor from the blood is converted into E1 and then catalyzed into E2 by 17␤-HSD1. Several studies have demonstrated the intratumoral expression of these enzymes involved in E2 biosynthesis and stressed the importance of aromatase in the intratumoral biosynthesis of E2. 14 -16 Thus, it is speculated that expression of these enzymes, especially aromatase, is enhanced in postmenopausal women as compared with premenopausal women in order to maintain the high E2 levels in tumors. However, it still remains to be established which enzyme(s) is responsible for the high E2 levels in tumors in postmenopausal women.In the present study, we measured the E2 and E1 levels in breast cancer tissues and investigated the association of the E2 and E1 levels with v...

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Section: Abstract: Breast Cancer; Estrogens; Aromatase; Sulfatase; 1mentioning

confidence: 99%

Involvement of up-regulation of 17?-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers

et al. 2001

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“…While postmenopausal women have low levels of circulating plasma estrogens, the local synthesis or intratumoral production of estrogens that takes place in breast carcinoma tissue itself can lead to higher estrogen levels in the tumor (1,2). Intratumoral production of estrogens occurs as a result of aromatization of C19 steroids such as androstenedione and testosterone into estrogens, and this is catalyzed by the cytochrome P450 aromatase enzyme (3)(4)(5).…”

Section: Introductionmentioning

confidence: 99%

Aromatase Localization in Human Breast Cancer Tissues: Possible Interactions between Intratumoral Stromal and Parenchymal Cells

Miki¹,

Suzuki²,

Tazawa³

et al. 2007

Cancer Research

117

145

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Aromatase is a key enzyme in intratumoral estrogen production required for the production of estrogens through the conversion of serum androgens in postmenopausal breast cancer patients. There have been, however, controversies regarding the intratumoral localization of aromatase in human breast carcinoma tissues. Therefore, we have first examined the intratumoral localization of aromatase mRNA/ protein in 19 breast carcinomas using laser capture microdissection/quantitative reverse transcription-PCR (RT-PCR) and immunohistochemistry. Aromatase mRNA and protein were detected in both intratumoral stromal and parenchymal cells in breast carcinoma tissues. Subsequent microarray expression profiling and clustering analyses, in addition to quantitative RT-PCR studies, showed a significant positive correlation between aromatase and estrogen-related receptor A mRNA expression in isolated carcinoma cells. We further examined an interaction between stromal cells isolated from human breast carcinoma tissues and breast carcinoma cell lines using a coculture system to study the biological characteristic of aromatase expression in carcinoma cells. Aromatase mRNA and enzyme activity and 17B-hydroxysteroid dehydrogenase type 1 mRNA in breast carcinoma cell lines, including MCF-7 and SK-BR-3 cells, were up-regulated in the presence of patient-derived 32N or 74T intratumoral stromal cells. The results from steroid conversion assays were also consistent with the findings above. The results of our study also showed that aromatase inhibitors were more effective in inhibiting aromatization induced by coculture in MCF-7 than that in stromal 32N. The examination of the localization of aromatase and its regulation, including the interactions existing between different cell types in human breast carcinoma tissues, may provide important information as to achieving better clinical response to aromatase inhibitors in breast cancer patients. [Cancer Res 2007;67(8):3945-54]

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“…The concentrations of estradiol (E2) in breast tissue from post-menopausal women are similar to those from pre-menopausal patients even though plasma E2 levels are 50-fold higher prior to the menopause [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. To explain this finding, several investigators have postulated that post-menopausal breast tissue converts androgens to estrogens in situ via the aromatase enzyme in amounts sufficient to maintain high tissue E2 levels [5,7,17].…”

Section: Introductionmentioning

confidence: 99%

Development of a high sensitivity, nested Q-PCR assay for mouse and human aromatase

Liu

Brenin

et al. 2007

Breast Cancer Res Treat

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Measurement of breast tissue estradiol levels could provide a powerful method to predict the risk of developing breast cancer but obtaining sufficient amounts of tissue from women is difficult from a practical standpoint. Assessment of aromatase in ductal lavage fluid or fine needle aspirates from breast might provide a surrogate marker for tissue estrogen levels but highly sensitive methods would be required. These considerations prompted us to develop an ultra-sensitive, "nested" PCR assay for aromatase which is up to one million fold more sensitive than standard PCR methods. We initially validated this assay using multiple tissues from the aromatase transgenic mouse and found that coefficients of variation for measurement of replicate samples averaged less than 5%. We demonstrated a 60-fold enhancement in aromatase message in the transgenic versus the wild type mouse breast but surprisingly, levels in the transgenic animals were highly variable, ranging from 0.4 to 27 relative units. The variability of aromatase expression in the transgenic breast did not correlate with the degree of breast development and did not appear to relate to hormonal manipulation of the MMTV promoter but probably related to lack of exhaustive inbreeding and mixed zygocity of transgenic animals. Extensive validation in mouse tissues provided confidence regarding the assay in human tissues, since nearly identical methods were used. The human assay was sufficiently sensitive to detect aromatase in a single human JAR (choriocarcinoma) cell, in all breast biopsies measured, and in 7/23 ductal lavage fluids.

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Concentration of endogenous oestradiol as related to oestradiol receptor sites in breast tumor cytosol

Cited by 55 publications

References 21 publications

Involvement of up-regulation of 17?-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers

Involvement of up-regulation of 17?-hydroxysteroid dehydrogenase type 1 in maintenance of intratumoral high estradiol levels in postmenopausal breast cancers

Aromatase Localization in Human Breast Cancer Tissues: Possible Interactions between Intratumoral Stromal and Parenchymal Cells

Development of a high sensitivity, nested Q-PCR assay for mouse and human aromatase

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