Type II oestrogen binding site is associated with the major 4S oestrogen receptor isoform in breast tumours

Marsigliante, Santo; Biscozzo, Luciana; Barker, Stewart; Leo, Giuseppe; Puddefoot, J. R.; Vinson, Gavin P.; Storelli, Carlo

doi:10.1016/0960-0760(92)90118-3

Cited by 7 publications

(4 citation statements)

References 18 publications

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“…The flavonoid quercetin that binds to the type II EBS exerts a potent inhibitory effects on the growth of these cell lines. It has been suggested that the presence of type II EBS has a prognostic value in the management of human breast cancer (35). Both our previous (17) and present studies demonstrated that the type II EBS is present in NPA cells, and that estradiol and flavonoids showed an antiproliferative effect on NPA cells in micromolar concentration.…”

Section: Discussionsupporting

confidence: 56%

Growth Inhibitory Effects of Flavonoids in Human Thyroid Cancer Cell Lines

Yin

Giuliano²,

Herle³

1999

Thyroid

105

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Previous studies have indicated that flavonoids exhibit antiproliferative properties on some hormone-dependent cancer cell lines, such as breast and prostate cancer. In the present study, the effects of some selected flavonoids, genistein, apigenin, luteolin, chrysin, kaempferol, and biochanin A on human thyroid carcinoma cell lines, UCLA NPA-87-1 (NPA) (papillary carcinoma), UCLA RO-82W-1 (WRO) (follicular carcinoma), and UCLA RO-81A-1 (ARO) (anaplastic carcinoma) have been examined. Among the flavonoids tested, apigenin and luteolin are the most potent inhibitors of these cell lines with IC50 (concentration at which cell proliferation was inhibited by 50%) values ranging from 21.7 microM to 32.1 microM. The cells were viable at these concentrations. Using NPA cells known to be estrogen receptor positive (ER+), it was shown that no significant [3H]-E2 displacement occurred with these flavonoids at the IC50 concentration. In WRO cells that are known to have an antiestrogen binding site (AEBS), biochanin A caused a stronger inhibitory growth effect (IC50 = 64.1 microM) than in NPA and ARO cells. In addition, it was observed that biochanin A has an appreciable binding affinity for the AEBS as indicated by the displacement of [3H]-tamoxifen from the WRO cells. In summary, flavonoids have potent antiproliferative activity in vitro against various human thyroid cancer cell lines. The inhibitory activity of certain flavonoid compounds may be mediated via the AEBS and/or type II EBS. The observation that ARO cells that lack both the AEBS and the ER are effectively inhibited by apigenin and luteolin suggest that other mechanisms of action are operative as well. The present study suggests that flavonoids may represent a new class of therapeutic agents in the management of thyroid cancer.

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Section: Discussionsupporting

confidence: 56%

Growth Inhibitory Effects of Flavonoids in Human Thyroid Cancer Cell Lines

Yin

Giuliano²,

Herle³

1999

Thyroid

105

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“…The increase in the level of low-affinity EBS (7.9 pmol/g) in uteri was 45-fold with an w20-fold increase in the specific activity (0.39 pmol/mg) of Estrogen receptors have been studied from a wide variety of tissue sources and cancer cell lines. Investigations in several laboratories during the last few years have clearly demonstrated the existence of two subtypes of estrogen receptors (1)(2)(3)(4)(5)(6)(7)(8). The two classes of estrogen receptors are differentiated with respect to their affinities toward estradiol binding: the high-affinity type I with a Kd of 0.1-1 nM and the low-affinity type II with a Kd .…”

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“…A majority ofthe studies to date have been done by using these sources of type II EBS. However, it has also been shown that the type II EBS appears present in certain breast tumor tissues (6,7) and in a wide variety of lymphoblastoid and endometrial cancers (22)(23)(24)(25)(26). Studies with type II EBS in extracts of estradiol-stimulated chicken oviduct and rat uteri demonstrated that estradiol binding to the low-affinity EBS is apparently cooperative in nature, as it displays a sigmoidal binding curve (1,2,8).…”

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confidence: 99%

“…The two classes of estrogen receptors are differentiated with respect to their affinities toward estradiol binding: the high-affinity type I with a Kd of 0.1-1 nM and the low-affinity type II with a Kd . :20 nM (3)(4)(5)(6)(7)(8) and generally termed as type II estrogen-binding site(s) (EBS). The structure and function of the high-affinity type I estrogen receptor has been the subject of a wide variety of extensive studies (9)(10)(11).…”

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confidence: 99%

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A low-affinity estrogen-binding site in pregnant rat uteri: analysis and partial purification.

Gray¹,

Biswas²,

Bashirelahi³

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

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We have identified a low-affinity (type U) estrogen-binding site (EBS) that is expressed at high levels durin pregnancy in rat uteri. Although this activity was dtectble I nonpegnt rat uteri, it was present in mounts (0.094 pmol/g of uteri) that were severalfold lower than the -affnity type I estrogen receptor (0.57 pmol/g of uteri). During prgnancy at 19-20 days of gestation, the low-affinity type II EBS became the mior (288%) esogen-binding ste in rat uteri. The increase in the level of low-affinity EBS (7.9 pmol/g) in uteri was 45-fold with an w20-fold increase in the specific activity (0.39 pmol/mg) of this form, whereas the hi h-anity form emaed relatively un (1, 2, 8).In this report we have demonstrated that the levels of a low-affinity EBS increase enormously during pregnancy in rat uteri, making pregnant rat uteri an abundant source of type II EBS. We also describe methodology for the purification of type II EBS from pregnant rat uteri to near homogeneity. MATERIALS AND METHODSMaterials. Pregnant and nonpregnant rats were obtained from Charles River Breeding Laboratories. Pregnant rats were sacrificed on the 19-20th day of gestation. The uteri were removed immediately after sacrifice, cleaned, frozen in liquid nitrogen, and stored at -800C until use. Rat uteri were gifts from I. Gewolb and J. Torday of the Department of Pediatrics.Steroid Binding and Scatchard Analysis. Single-point steroid-binding measurement was used to monitor the purification of type H EBS with the hydroxyapatite method (27). A standard 100-A4 binding mixture contained 25 nM [3H]estradiol, 10 mM Tris'HCl (pH 7.4), 1.5 mM EDTA, 2% glycerol, and samples as indicated. The binding reactions were allowed to incubate for 15 min at room temperature followed by chilling in an ice/water slurry for 5 min. The remainder ofthe assay followed the standard hydroxyapatite method, as described (27). Saturation binding and competition analyses were also done by using a modification of this assay.Preparation of Type I and Type U EBS Extrc. Preparation of cytosol from rat uteri and (NH4)2SO4 fractionation were done essentially as described (8

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Evidence of Type Ii Estrogen Receptor in Human Osteoblast‐like Cells

Toesca

Pagnotta

Specchia

2000

Cell Biology International

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Osteoblast-like cells isolated from human bone bioptic specimens were characterized and analysed for the presence of type II estrogen receptor (type II EBS). The amount of type II EBS was measured by a whole-cell assay at 4 degrees C for 2.5 h using [(3)H]-estradiol as tracer. Saturation analysis, used to investigate the binding characteristic of type II EBS, resulted in a sigmoid curve. Scatchard analysis showed the binding affinity of the estrogen receptor, yielding a concave plot. The dissociation constant (K(d)), determined from the [(3)H]-estradiol concentration required for half saturation was about 12+/-2 nM (SD). The number of type II EBS, estimated at maximum binding, was 197,000+/-8800 sites per cell. If the regulation of the receptor by flavonoids would be confirmed, the evidence of type II EBS in osteoblast-like cells could suggest a direct action of ipriflavone and others flavonoids on bone density in postmenopausal osteoporosis.

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Type II oestrogen binding site is associated with the major 4S oestrogen receptor isoform in breast tumours

Cited by 7 publications

References 18 publications

Growth Inhibitory Effects of Flavonoids in Human Thyroid Cancer Cell Lines

Growth Inhibitory Effects of Flavonoids in Human Thyroid Cancer Cell Lines

A low-affinity estrogen-binding site in pregnant rat uteri: analysis and partial purification.

Evidence of Type Ii Estrogen Receptor in Human Osteoblast‐like Cells

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