Detection of breast cancer-associated estrone sulfatase in breast cancer biopsies and cell lines using polymerase chain reaction

Evans, T.R. Jeffry; Rowlands, Martin; Luqmani, Yunus A.; Chander, Surinder K.; Coombes, R. Charles

doi:10.1016/0960-0760(93)90294-7

Cited by 23 publications

(1 citation statement)

References 24 publications

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“…In order to verify the role of SOAT for the E 1 S-dependent proliferation of breast cancer cells, we intended to generate an in vitro model that mimics the in vivo situation as near as possible. Different ER positive breast cancer cell lines such as T47D and MCF7 have emerged as in vitro models for proliferation studies in the past ( MacIndoe, 1988 ; Pasqualini et al, 1990 ; Evans et al, 1993 ; Billich et al, 2000 ; Schmitt et al, 2001 ; Maggiolini et al, 2001 , 2002 ). Of those, we used T47D cells, as their intracrine estrogen synthesis is well characterized and E 1 S uptake carrier expression has been investigated previously on these cells ( Pizzagalli et al, 2003 ; Nozawa et al, 2004 ; Miki et al, 2006 ).…”

Section: Discussionmentioning

confidence: 99%

Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6)

et al. 2018

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Estrogens play a pivotal role in the development and proliferation of hormone-dependent breast cancer. Apart from free estrogens, which can directly activate the estrogen receptor (ER) of tumor cells, sulfo-conjugated steroids, which maintain high plasma concentrations even after menopause, first have to be imported into tumor cells by carrier-mediated uptake and then can be cleaved by the steroid sulfatase to finally activate ERs and cell proliferation. In the present study, expression of the sodium-dependent organic anion transporter SOAT was analyzed in breast cancer and its role for hormone-dependent proliferation of T47D breast cancer cells was elucidated. The SOAT protein was localized to the ductal epithelium of the mammary gland by immunohistochemistry. SOAT showed high expression in different pathologies of the breast with a clear ductal localization, including ductal hyperplasia, intraductal papilloma, and intraductal carcinoma. In a larger breast cancer cDNA array, SOAT mRNA expression was high in almost all adenocarcinoma specimen, but expression did not correlate with either the ER, progesterone receptor, or human epidermal growth factor receptor 2 status. Furthermore, SOAT expression did not correlate with tumor stage or grade, indicating widespread SOAT expression in breast cancer. To analyze the role of SOAT for breast cancer cell proliferation, T47D cells were stably transfected with SOAT and incubated under increasing concentrations of estrone-3-sulfate (E1S) and estradiol at physiologically relevant concentrations. Cell proliferation was significantly increased by 10-9 M estradiol as well as by E1S with EC50 of 2.2 nM. In contrast, T47D control cells showed 10-fold lower sensitivity to E1S stimulation with EC50 of 21.7 nM. The E1S-stimulated proliferation of SOAT-T47D cells was blocked by the SOAT inhibitor 4-sulfooxymethylpyrene. In conclusion: The present study clearly demonstrates expression of SOAT in breast cancer tissue with ductal localization. SOAT inhibition can block the E1S-stimulated proliferation of T47D breast cancer cells, demonstrating that SOAT is an interesting novel drug target from the group of E1S uptake carriers for anti-proliferative breast cancer therapy.

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Section: Discussionmentioning

confidence: 99%

Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6)

et al. 2018

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Stilbene‐Based Inhibitors of Estrone Sulfatase with a Dual Mode of Action in Human Breast Cancer Cells

Walter

Liebl

Angerer

2004

Archiv der Pharmazie

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Estrone sulfate (E1S) is an endogenous prodrug that delivers estrone and, subsequently, estradiol to target cells, after hydrolysis by the enzyme estrone sulfatase, which is active in various tissues including hormone-dependent breast cancer. Blockade of this enzyme should reduce the estrogen level in breast cancer cells and prevent hormonal growth stimulation. In this study, a number of sulfamoyloxy-substituted stilbenes with side chains that guarantee antiestrogenic activity were synthesized and evaluated as inhibitors of estrone sulfatase. They inhibited this enzyme in human MDA-MB 231 breast cancer cells, with IC(50) values in the submicromolar range. The effects of both the free hydroxy derivatives and the sulfamates on gene activation were determined in transfected MCF-7/2a breast cancer cells stimulated either with estradiol or with estrone sulfate. The analysis of data revealed a dual mode of action of the majority of compounds. They blocked gene expression by inhibition of estrone sulfatase and by antiestrogenic action. This pharmacological profile was also observed in assays on antiproliferative activity. The most potent derivative 8 g inhibited the growth of wild-type human MCF-7 cells with an IC(50) value of 13 nM.

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Inhibition of steroid sulfatase activity and cell proliferation in ZR-75-1 and BT-474 human breast cancer cells by KW-2581 in vitro and in vivo

Ishida

Nakata

Sato

et al. 2006

Breast Cancer Res Treat

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In the present study, we found that two hormone receptor-positive human breast cancer cell lines, ZR-75-1 and BT-474, naturally expressed steroid sulfatase (STS) protein and had catalytic activity to produce estrone from estrone sulfate (E1S) with a comparable level to those in human breast cancer tissues. E1S at physiological concentrations stimulated the growth of those cells. A novel steroidal STS inhibitor, KW-2581 inhibited the STS activity of ZR-75-1 cells with an IC(50) of 13 nM, a potency equal to or higher than that of the non-steroidal STS inhibitor, 667 COUMATE. The inhibitory effect of KW-2581 was enhanced by pre-incubation with STS enzyme, suggests being irreversible inhibition. KW-2581 inhibited the E1S-stimulated growth of ZR-75-1 cells with an IC(50) of 0.18 nM, but failed to inhibit the growth stimulated by 17beta-estradiol. Expression of E1S-induced progesterone receptors in ZR-75-1 cells was reduced by treatment of KW-2581 at concentrations as low as 0.1 nM. Oral administration of KW-2581 for 4 weeks caused tumor shrinkage in a mouse xenograft model. Tumor STS activity had been completely (>95%) eliminated by 24 hours after the last administration. These findings suggest that KW-2581 has considerable potential for therapeutic development as a novel anti-hormonal drug for treatment of breast cancer.

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Detection of breast cancer-associated estrone sulfatase in breast cancer biopsies and cell lines using polymerase chain reaction

Cited by 23 publications

References 24 publications

Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6)

Estrone-3-Sulfate Stimulates the Proliferation of T47D Breast Cancer Cells Stably Transfected With the Sodium-Dependent Organic Anion Transporter SOAT (SLC10A6)

Stilbene‐Based Inhibitors of Estrone Sulfatase with a Dual Mode of Action in Human Breast Cancer Cells

Inhibition of steroid sulfatase activity and cell proliferation in ZR-75-1 and BT-474 human breast cancer cells by KW-2581 in vitro and in vivo

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