Oestrone sulphate, adipose tissue, and breast cancer

Hawkins, R. A.; Thomson, Marian; Killen, E.

doi:10.1007/bf01806013

Cited by 34 publications

(8 citation statements)

References 43 publications

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“…After 45 min of incubation STS activity was not significantly decreased in comparison to 15 min of incubation. Various Km for STS activity have been reported by others ranging from 4 to 27 M in human BC tissue [34,35,[54][55][56], 5.8 M in dysplastic human breast tissue [52], and from 4.1 to 18.2 M in normal human breast tissue homogenates [57]. V max for STS activity has been reported to range between 0.8 and 125 mol E 1 /(g(protein) h) in human BC tissue [35], and between 18.2 and 75.9 mol E 1 /g in normal breast tissue homogenates [57].…”

Section: Discussionmentioning

confidence: 96%

Effects of black cohosh on estrogen biosynthesis in normal breast tissue in vitro

Stute¹,

Nisslein

Götte³

et al. 2007

Maturitas

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Objectives: To investigate the effect of black cohosh on the estrogen biosynthesis in the breast in vitro. Methods: Steroid sulfatase (STS) activity was studied in normal breast tissue obtained from pre-and postmenopausal women undergoing reduction mammoplasty. STS protein expression was studied by immunohistochemistry and western blotting. Breast tissue was incubated in vitro without or with black cohosh (iCR) at concentrations ranging from 0.1 mg/ml to 1 ng/ml. STS activity was evaluated by incubating homogenized breast tissue with [ 3 H]-estrone sulfate, separating the formed products, estrone (E 1 ) and estradiol (E 2 ), by thin layer chromatography and measuring the amounts of E 1 and E 2 by scintillation counting. Results: STS protein expression and enzymatic activity were detected in all specimens investigated. In all groups, significantly more E 1 than E 2 was produced. Local estrogen formation was decreased in premenopausal breast tissue by treatment with iCR at 0.1 mg/ml (p ≤ 0.05). Conclusions: iCR decreases local estrogen formation in normal human breast tissue in vitro. This may contribute to the lack of hormonal effects of black cohosh in breast tissue observed in previous studies.

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Section: Discussionmentioning

confidence: 96%

Effects of black cohosh on estrogen biosynthesis in normal breast tissue in vitro

Stute¹,

Nisslein

Götte³

et al. 2007

Maturitas

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“…For example, some authors used intact cells [25,37,38,[42][43][44][45][46][47][48][49][50][51], others cell homogenates [39,50]. Similarly, after having added the substrate 3 [14,22,[53][54][55], 5.8 lM in dysplastic human breast tissue [55], and 5.6-10.0 lM in MCF-7 cells [35,43,46]. V max for STS activity has been reported to range from 0.8 to 125 lmol E1/g of protein/h in human breast cancer tissue [14], and from 1.6 to 5.2 nmol E1/mg protein/h in MCF-7 cells [35,43,46].…”

Section: Discussionmentioning

confidence: 99%

Differential effect of hormone therapy on E1S-sulfatase activity in non-malignant and cancerous breast cells in vitro

Stute

Götte

Kiesel

2007

Breast Cancer Res Treat

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Breast tissue possesses the enzymes for local estrogen biosynthesis. We measured the effect of Estradiol (E2), Tibolone (OrgOD14) and its metabolite Org4094 on estrone sulfate (E1S)-sulfatase (STS) using breast cancer (MCF-7) and non-malignant breast cells (HBL-100). Cells were cultured in 5% steroid depleted fetal calf serum for 3 days and subsequently incubated with each steroid for either 24 h or directly in cell extracts. STS mRNA and protein expression, and its subcellular localization were determined by semi-quantitative RT-PCR, immunoblotting, and confocal immunofluorescence microscopy. STS activity was evaluated by incubating homogenized breast cells with [(3)H]-E1S. The products E1 and E2 were separated by thin layer chromatography. STS was co-localized with the Golgi marker protein GM130 and the endoplasmic reticulum marker protein calnexin. Treatment did not significantly alter STS mRNA expression. STS protein expression was increased by each steroid in HBL-100 cells but by E2 only in MCF-7 cells. 24 h incubation with OrgOD14 and Org4094 did not alter STS activity in both cell lines. However, STS activity was significantly diminished in HBL-100 but slightly increased in MCF-7 cells by 24 h treatment with E2. "Direct" incubation of cell extracts, eliminating cellular regulation of metabolism, reduced estrogen biosynthesis regardless of cell line and treatment. In conclusion, the immediate reduction of estrogen biosynthesis by OrgOD14 is counteracted by an increased STS protein expression. On the contrary, E2 exerts a differential effect on STS in HBL-100 and MCF-7 cells. The transition from normal to malignant breast cells may be accompanied by an abolished autoregulation of local estrogen formation.

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“…Thus, there is a need for readily available techniques for studying the normal breast. Compared with other ex vivo culture methods, such as tissue slices (Hawkins et al 1985), the whole breast tissue model may be applied to study the effects of exogenous substances for up to 1 week in culture. Investigations of the biology of the human breast may be conducted with preserved tissue architecture and without the use of an artificial extracellular matrix.…”

Section: Discussionmentioning

confidence: 99%

Estradiol increases VEGF in human breast studied by whole-tissue culture

Garvin¹,

Nilsson²,

Huss

et al. 2006

Cell Tissue Res

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Sex steroid exposure constitutes a risk factor for breast cancer, but little is known about the effects of sex steroids on the normal breast, largely because of the lack of convenient models. We have developed a method of culturing normal breast tissue ex vivo. We have applied this method to investigate the effects of estradiol and progesterone on the key angiogenic mediator, vascular endothelial growth factor (VEGF), in the breast. Whole breast tissue was obtained from routine reduction mammoplasty. Tissue biopsies were cultured in vitro for 1-3 weeks, and the expression of luminal cytokeratin 18 was determined by immunohistochemistry. As an application, tissue biopsies were treated in vitro for 1 week with or without estradiol or estradiol and progesterone. Estrogen receptor, progesterone receptor, and Ki-67 were analyzed, and VEGF levels were examined by quantitative immunoassay and immunohistochemistry. Whole breast tissue was cultured ex vivo for 1 week with preserved morphology. Increased detachment of the luminal epithelium was observed after 2 weeks. Estradiol increased extracellular levels of VEGF in normal breast tissue biopsy medium. The addition of progesterone had neither stimulatory nor inhibitory effects on secreted VEGF. The method of whole breast tissue culturing thus provide a means by which to explore the biology of normal breast tissue. Our results suggest that estradiol exerts pro-angiogenic effects in normal breast by increasing levels of biologically active VEGF.

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Oestrone sulphate, adipose tissue, and breast cancer

Cited by 34 publications

References 43 publications

Effects of black cohosh on estrogen biosynthesis in normal breast tissue in vitro

Effects of black cohosh on estrogen biosynthesis in normal breast tissue in vitro

Differential effect of hormone therapy on E1S-sulfatase activity in non-malignant and cancerous breast cells in vitro

Estradiol increases VEGF in human breast studied by whole-tissue culture

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