Estrogen Receptors in Human Breast Cancer

McGuire, William

doi:10.1172/jci107175

Cited by 332 publications

(102 citation statements)

References 13 publications

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“…Human tumours in immunodeficient host animals represent a complex model; steroid hormones modulate the residual immune system, influence the endocrine milieu and alter the stroma. E 2 -treatment could enhance tumour growth by modulating the host to produce other growth factors (McGuire et al, 1975). Conversely, growth of cells within the tumour mass may be affected by interactions between malignant cells and the surrounding stroma.…”

Section: Discussionmentioning

confidence: 99%

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17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

et al. 2002

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The putative oestrogen receptor negative human breast cancer cell line MDA231, when grown as tumours in mice continually receiving 17b-oestradiol, showed substantially increased growth rate when compared to control animals. Further, we observed that 17b-oestradiol treatment could both increase the growth rate of established MDA231 tumours as well as decreasing the time taken for initiating tumour growth. We have also demonstrated that this increase in growth rate is accompanied by a four-fold increase in nitric oxide synthase activity, which was predominantly the inducible form. Inducible-nitric oxide synthase expression in these tumours was confirmed by immunohistochemical analysis and appeared localized primarily in areas between viable and necrotic regions of the tumour (an area that is presumably hypoxic). Prophylactic treatment with the nitric oxide synthase inhibitor nitro-L-arginine methyl ester resulted in significant reduction in this apparent 17b-oestradiol-mediated growth promoting effect. Tumours derived from mice receiving 17b-oestradiol-treatment were characterized by a significantly lower fraction of perfused blood vessels and an indication of an increased hypoxic fraction. Consistent with these observations, 17b-oestradiol-treated tumours were less radio-responsive compared to control tumours when treated with a single radiation dose of 15 Gy. Our data suggests that long-term treatment with oestrogen could significantly alter the tumour oxygenation status during breast tumour progression, thus affecting response to radiotherapy.

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Section: Discussionmentioning

confidence: 99%

“…They have also been implicated in promoting the growth of most oestrogen-receptor (ER) positive mammary carcinomas through their mitogenic effects on the cells via these receptors (McGuire et al, 1975;Dickson and Lippman, 1987). It is proposed that 17b-oestradiol (E 2 ) enters the target cells and binds to nuclear ER.…”

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17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

et al. 2002

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“…(Folca, Glascock and Irvine 1961;Jensen et al, 1971;McGuire et al, 1975). We have, therefore, investigated the reproducibility of receptor measurements and the role of morphological factors in determiining variations in receptor concentration.…”

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confidence: 99%

Reproducibility of measurements of oestrogen-receptor concentration in breast cancer

Hawkins¹,

Hill²,

Freedman³

et al. 1977

Br J Cancer

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Summary.-The reproducibility of measurements of oestrogen-receptor activity has been examined in multiple specimens from a rabbit uterus, a rat mammary tumour and human breast tumours. The relationship between receptor concentration and tumour histology has also been investigated in 11 large primary tumours.In the animal tissues, receptor measurements were relatively reproducible (co- In the 11 primary breast cancers selected for study, the level of receptor activity was related to menopausal status and the tumour content of the specimen.We conclude that the receptor activity detected varies within a tumour and depends upon the tumour content of the biopsy specimen. Predictions based on precise quantitation of receptor concentrations may therefore necessitate replicate tumour sampling and correction for the fraction of non-tumour tissue in each sample.CURRENTLY, the best index of the hormonal sensitivity of a breast cancer is the concentration of oestrogen-receptor protein in the cytoplasm of the tumour. (Folca, Glascock and Irvine 1961;Jensen et al., 1971;McGuire et al., 1975). We have, therefore, investigated the reproducibility of receptor measurements and the role of morphological factors in determiining variations in receptor concentration. MATERIALS AND METHODSTissues.-To examine the precision of the receptor assay, multiple (4-8) portions were cut at 0-40C, from each of 4 tissues selected for their apparent homogeneity. These tissues 'were the uterus from a non-pregnant rabbit, a rat mammary carcinoma (generated by the intragastric administration of 30 mg dimethylbenz(a)anthracene at 50 days of age) a large, cellular, intracanalicular fibroadenoma removed surgically from a 59-year-old woman, and a lymplh node which had been largely replaced by anaplastic breast carcinoma from a 75-year-old woman. Each portion of tissue was assayed for oestrogen-receptor activity.To examine the reproducibility of receptor measurements in human breast cancer an(d relate this to morphology, 11 mastectomy specimens containing large, primary breast cancers were collected on ice. Each tumour wTas excised from the breast, measured and sectioned into 2-3 cubes. Each cube was divided into 2, one portion being used for histological examination, the other for oestrogen-receptor assay.Oe8trogen-receptor activity was determined by the method of Hawkins, Hill and Freedman (1975). A portion (160 >mg) of fat-free tumour was homogenized in tris buffer (0-25 M sucrose, 10 mM tris and 1 mM ethylene diamine tetra-acetate) at the rate of 100 mg/ml for 3 x 15 s, with intervals for cooling between periods of homogenization.

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“…Ovariectomy, adrenalectomy and hypophysectomy have been used to curtail the growth of some breast tumours, while more recently oestrogenreceptor analysis has been used to identify tumours most likely to respond to hormonal manipulation (Beatson, 1896;Jensen et al, 1971;McGuire et al, 1975). Oestrogen-dependent tumours have been described (Caldwell et al, 1971) and it is now well documented that oestrogens can stimulate the development of breast tumours once they have been induced (King, 1971).…”

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Faecal bile acids and clostridia in patients with breast cancer

Murray¹,

Blackwood²,

Calman³

et al. 1980

Br J Cancer

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Summary.-We have studied 30 patients presenting with breast cancer and 36 control patients admitted to hospital for minor surgery. Stool specimens were obtained for bile acid analysis and bacterial nuclear dehydrogenation activity (NDC) estimation.The mean total faecal bile acid (FBA) concentration (,tmol/g) in patients with breast cancer was 15-6 + 1-8 s.e., significantly lower than for control patients (20.5 + 1-9).NDC were isolated from the faeces of 58% of breast cancer patients and 15% of control patients, this difference being statistically highly significant (P < 0.005). Increased bileacid degradation by bacteria in the large bowel may explain the reduced FBA concentration in patients with breast cancer. Increased NDC isolation in breast-cancer patients suggests that oestrogen production in the colon may play a role in the aetiology of breast cancer in some patients.

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Estrogen Receptors in Human Breast Cancer

Cited by 332 publications

References 13 publications

17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

17β-Oestradiol treatment modulates nitric oxide synthase activity in MDA231 tumour with implications on growth and radiation response

Reproducibility of measurements of oestrogen-receptor concentration in breast cancer

Faecal bile acids and clostridia in patients with breast cancer

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