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

Chétrite, G.; Cortés-Prieto, J; Philippe, Jean-Claude; Wright, Françoise; Pasqualini, Jörge R.

doi:10.1016/s0960-0760(00)00040-6

Cited by 258 publications

(222 citation statements)

References 22 publications

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“…For example, the mean concentration of E2 in the breast tumors of premenopausal patients was approximately 1.2 pmol/g tissue (that means that if the density of tumor is 2 g/mL, the in situ E2 concentration will be 2.4 nmol/L), whereas a plasma E2 concentration of approximately 0.22 nmol/L was reported in the same paper [4,5] . Similar results were obtained from other previous studies [6,7] and from our current study on MCF-7 xenograft tumors (0.36-0.48 nmol/L). However, we once investigated the effect of TM208 on SULT1A1 and SULT2A1 and found that TM208 induced the expression of SULT1A1 more significantly than that of SULT2A1 in both MCF-7 cells and MCF-7 xenograft tumors, but all of the observed increases were less than 4-fold (Figure S1-S2).…”

Section: Discussionsupporting

confidence: 93%

“…These data are neither significantly different from each other nor from the E2 level in the normal mammary fat pad (0.39±0.01 nmol/L). The absolute reduced intratumoral E2 concentration in the TM208 treatment group is not as much as the levels observed in situ for the human breasts of healthy women versus patients [4,6,7] , but the difference was statistically significant, and all the tested concentrations were within the physiological range of E2 concentration. To the best of our knowledge, we are the first group to detect the intratumoral E2 concentration in MCF-7 xenograft mice.…”

Section: Discussionmentioning

confidence: 58%

“…Therefore, intratumoral estrogens, especially 17β-estradiol (E2), play pivotal roles in the proliferation and development of hormone-dependent breast carcinoma cells [1][2][3] . Previous studies have demonstrated that the tissue concentra-tions of E2 in breast carcinomas are much higher than those found in the plasma [4,5] or normal mammary tissues [6,7] . Consequently, blocking in situ estrogen production appears to be a potent breast cancer treatment [8][9][10][11] .…”

Section: Introductionmentioning

confidence: 89%

“…Among these isoforms, estrogen sulfotransferase (EST, SULT1E1) plays the most important role in estrogen inactivation under physiological conditions due to its high affinity for estrogens [15] . In most previous studies, the intratumoral estrogen concentrations were expressed as pg/g tissue or pmol/g tissue, which can be approximately calculated at the "nanomolar" (physiological) level even if they are much higher than those found in normal mammary tissues [6,7] or plasma [4,5] . Therefore, the intratumoral sulfation of estrogen is mainly catalyzed by EST rather than other SULT isoforms.…”

Section: Introductionmentioning

confidence: 99%

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Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Chen

Song

et al. 2015

Acta Pharmacol Sin

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Aim: Sulfotransferase-catalyzed sulfation is the most important pathway for inactivating estrogens. Thus, activation of estrogen sulfotransferase (EST) may be an alternative approach for the treatment of estrogen-dependent breast cancer. In this study we investigated the involvement of EST in anti-breast cancer effects of the dithiocarbamate derivative TM208 in vitro and in vivo. Methods: The viability of human breast cancer MCF-7 cells was determined using a SBB assay. Nude mice bearing MCF-7 cells were orally administered TM208 (50 and 150 mg·kg -1 ·d -1 ) for 18 days. The xenograft tumors and uteri were collected. The mRNA expression of EST was examined with real-time PCR. EST protein was detected with Western blot, ELISA or immunohistochemical staining assays. A radioactive assay was used to measure the EST activity. Uterotropic bioassay was used to examine the uterine estrogen responses. Results: Treatment with TM208 (10, 15 and 20 µmol/L) concentration-dependently increased EST expression in MCF-7 cells in vitro. Co-treatment with triclosan, an inhibitor of sulfonation, abolished TM208-induced cytotoxicity in MCF-7 cells. TM208 exhibited an apparent anti-estrogenic property: it exerted more potent cytotoxicity in E2-treated MCF-7 cells. In the nude mice bearing MCF-7 cells, TM208 administration time-dependently increased the expression and activity of EST, and blocked the gradual increase of E2 concentration in the xenograft tumors. Furthermore, TM208 administration blocked the estrogens-stimulated uterine enlargement. Tamoxifen, a positive control drug, produced similar effects on the expression and activity of EST in vitro and in vivo. Conclusion: The induction of EST and reduction of estrogen concentration contribute to the anti-breast cancer action of TM208 and tamoxifen. TM208 may be developed as anticancer drug for the treatment of estrogen receptor-positive breast cancer.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 58%

Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Chen

Song

et al. 2015

Acta Pharmacol Sin

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“…In blood, elevated levels of estrogen were associated with the increased risk for breast cancer in both pre-and postmenopausal women (46,47). Furthermore, higher concentrations of estrogen were found in breast tumor tissue compared to normal breast tissue (48)(49)(50). Approximately two-thirds of all breast cancer patients were positive for ER, and could benefit from hormone therapy, but up to 50% of these cases had either de novo resistance or developed resistance during treatment (51,52).…”

Section: Estrogen and Breast Cancermentioning

confidence: 99%

Hormonal regulation of immune modulators in human breast tissue

Morad¹

2015

Linköping University Medical Dissertations

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Breast cancer is the most common form of cancer and the second leading cause of malignancy-associated death in women worldwide. Estrogens are the main sex hormones in women. They are essential for the development and function of normal breast mammary glands; however, prolonged exposure to estrogens increases the risk of breast cancer development and progression. Approximately two-thirds of all breast cancer patients are positive for estrogen receptor (ER), but only 50% of those cases can benefit from antiestrogen therapy. In this thesis we investigated the effects of estrogen, diet modification, and anti-estrogen drugs on several immune modulators in normal human breast tissue. We used the microdialysis technique to sample the immune modulators in situ in normal human breast tissue, in malignant breast tissue, and in tumor tissue from both the immune competent mice with murine breast cancer and immune deficient mice bearing human breast tumors. Furthermore, we also used ex vivo culture of normal breast tissue and in vitro cell culture of breast cancer cell lines. A combined cell culture (co-culture) of breast cancer cell lines, together with the primary mature adipocytes, was also used in this thesis. In Paper I and Paper II, our results suggested that estrogen exerted both proinflammatory and pro-tumorigenic effects in normal human breast tissue. Estradiol increased extracellular interleukin-1β (IL-1β) and leptin levels and decreased IL-1Ra and adiponectin levels in normal human breast tissue. In contrast, tamoxifen decreased IL-1β and leptin levels and increased IL-1Ra and adiponectin levels, shifting the environment towards an antiinflammatory and antitumorigenic state. Diet modification with flaxseed for 30 days also increased IL-1Ra levels, creating an anti-inflammatory environment in normal breast tissue. In the breast cancer tissue, we found that extracellular IL-1β levels and leptin levels were significantly higher, whereas adiponectin levels were significantly lower, compared with normal adjacent breast tissue, which suggested a more proinflammatory state. In the third paper, our in vivo investigation of normal breast tissue revealed significant correlations between vascular endothelial growth factor (VEGF) and leptin, IL-1β and leptin, and between VEGF and IL-1β. No correlations were found in the abdominal subcutaneous (s.c.) fat tissue. Our in vitro inhibition experiments suggested that VEGF was a potent regulator of leptin, but that leptin was not a potent regulator of VEGF. Co-culture per se altered the release of VEGF and leptin and enhanced the effects of estradiol, compared with monocultures of the included cell types. In conclusion, the results presented in this thesis will increase the overall understanding of the role of estrogens in breast cancer, which may be useful in future treatment studies

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Sulfation of vitamin D₃‐related compounds—identification and characterization of the responsible human cytosolic sulfotransferases

et al. 2017

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While 25-hydroxyvitamin D 3-O-sulfate is known to be present in circulation, how it is generated in the body remains unclear. This study aimed to investigate its sulfation in major human organs and to unveil the responsible cytosolic sulfotransferases (SULTs). Of the vitamin D -related compounds tested, 25-hydroxyvitamin D and 7-dehydrocholesterol are preferentially sulfated by human organ cytosols. Among the 13 human SULTs, SULT2A1 shows sulfating activity toward all vitamin D -related compounds, whereas SULT1A1 and SULT2B1a/SULT2B1b show sulfating activity exclusively for, respectively, calcitriol and 7-dehydrocholesterol. These findings suggest that the metabolic pathway leading to the formation of 25-hydroxyvitamin D 3-O-sulfate may be mediated by the sulfation of 25-hydroxyvitamin D or by the conversion of 7-dehydrocholesterol-3-O-sulfate in the skin.

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

Cited by 258 publications

References 22 publications

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Hormonal regulation of immune modulators in human breast tissue

Sulfation of vitamin D₃‐related compounds—identification and characterization of the responsible human cytosolic sulfotransferases

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

Cited by 258 publications

References 22 publications

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Intratumoral estrogen sulfotransferase induction contributes to the anti-breast cancer effects of the dithiocarbamate derivative TM208

Hormonal regulation of immune modulators in human breast tissue

Sulfation of vitamin D3‐related compounds—identification and characterization of the responsible human cytosolic sulfotransferases

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Sulfation of vitamin D₃‐related compounds—identification and characterization of the responsible human cytosolic sulfotransferases