17 β -Hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma: a correlation to clinicopathological parameters

Suzuki, Takashi; Moriya, Takuya; Ariga, Naohiro; Kaneko, Chika; Kanazawa, Mimari; Sasano, Hironobu

doi:10.1054/bjoc.1999.0956

Cited by 115 publications

(107 citation statements)

References 33 publications

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“…A few immunohistochemical studies of 17HSD type 1 in human breast cancer have been reported, suggesting that 17HSD type 1 may play an important role in the in situ regulation of oestradiol production in hormone-dependent breast carcinomas (Poutanen et al, 1992;Sasano et al, 1996;Suzuki et al, 2000). In a previous study, we found that the expression of both 17HSD types 1 and 2 differ in the tumours of patients with and without late relapse in the disease (Gunnarsson et al, 2001).…”

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confidence: 65%

17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

2005

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The 17b-hydroxysteroid dehydrogenase (17HSD) enzymes are involved in the local regulation of sex steroids. The 17HSD type 1 enzyme catalyses the interconversion of the weak oestrone (E1) to the more potent oestradiol (E2), whereas 17HSD type 2 catalyses the oxidation of E2 to E1. The aim of this study was to correlate the expression of these enzymes in the tumour with the recurrence-free survival of tamoxifen-treated breast cancer patients. We used real-time reverse transcriptase PCR to investigate the mRNA expression of 17HSD types 1 and 2 in tumour samples from 230 postmenopausal patients. For the patients with oestrogen receptor (ER)-positive breast cancer, we found a statistically significant positive correlation between recurrence-free survival and expression of 17HSD type 2 (P ¼ 0.026). We examined the ratio of 17HSD types 2 and 1, and ER-positive patients with low ratios showed a significantly higher rate of recurrence than those with higher ratios (P ¼ 0.0047). ER positive patients with high expression levels of 17HSD type 1 had a significantly higher risk for late relapse (P ¼ 0.0051). The expression of 17HSD types 1 and 2 in breast cancer differs from the expression of these enzymes in normal mammary gland, and this study indicates that the expression has prognostic significance in breast cancer.

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confidence: 65%

17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

2005

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“…Suzuki et al 20 reported no significant correlation of 17␤-HSD1 expression determined by immunohistochemistry with menopausal status. The reason for this discrepancy is currently unknown, but immunohistochemistry is an essentially qualitative examination and is not suitable for the comparison of protein expression levels between samples.…”

Section: Discussionmentioning

confidence: 98%

“…The reason for this discrepancy is currently unknown, but immunohistochemistry is an essentially qualitative examination and is not suitable for the comparison of protein expression levels between samples. In Suzuki et al's report, 20 a validation study demonstrating that immunohistochemistry can be used for the qualitative analysis of 17␤-HSD1 protein expression was lacking. Ideally, immunohistochemical results should have been compared with those obtained by Western blot or bioassay.…”

Section: Discussionmentioning

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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“…17β-HSD1 is described to be overexpressed at mRNA level in breast cancer tissue [10][11][12] and endometriotic lesions. [13] Since a more local mode of action can be anticipated compared to existing medical treatments, its selective inhibition is regarded as a promising strategy for the treatment of EDD, with the prospect of less side effects.…”

Section: Figurementioning

confidence: 99%

Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker

Abdelsamie

Bey²,

Hanke³

et al. 2014

European Journal of Medicinal Chemistry

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17 β -Hydroxysteroid dehydrogenase type 1 and type 2 in human breast carcinoma: a correlation to clinicopathological parameters

Cited by 115 publications

References 33 publications

17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

17β-Hydroxysteroid dehydrogenases involved in local oestrogen synthesis have prognostic significance in breast cancer

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

Inhibition of 17β-HSD1: SAR of bicyclic substituted hydroxyphenylmethanones and discovery of new potent inhibitors with thioether linker

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