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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oestrogen predominance over progesterone may cause hyperproliferation of mammary epithelium and thus promote breast carcinogenesis. In patients with a hormone-dependent tumour, oestrogens may also accelerate cancer growth. Conversely, they may inhibit tumour growth in patients with an oestrogen receptor-negative carcinoma which has grown in an oestrogen-poor environment. Progesterone opposes oestrogen-induced epithelial proliferation and causes cellular differentiation with decreased mitosis, thus reducing the risk of breast cancer. Prolactin brings about mammary epithelial differentiation for secretory function; in the lactation state, epithelial proliferation is minimal. The role of androgens, melatonin, thymosin, metabolic hormones (growth hormone, thyroid hormone(s), insulin, glucocorticosteroids) and prostaglandins in the pathobiology of breast cancer is poorly understood. A breast cancer population consists of individuals in whom more than 20 different tumour subsets may be present, i.e. patients with different individual tumour pathobiology and endocrinology patterns and therefore different prognoses. Progress in the endocrinology of breast cancer seems possible through prospective studies in which hormones are determined in normal breast tissue (ductal fluid, cyst fluid) and then related to the corresponding concentrations in the plasma and urine of patients who develop breast cancer and those who do not. In addition, genetic and nonhormonal risk factors for breast cancer must be taken into consideration to define the endocrinological aspects involved.
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PMID:Endocrinology of breast cancer. 330 71

Serum levels of the two lactogenic hormones prolactin (PRL) and growth hormone (GH) were compared when determined by radioimmunoassay (RIA) and two-site immunoradiometric (IRMA) assays in 83 normal premenopausal women. The mean values for the PRL and GH results determined by RIA were higher than those obtained by IRMA, despite strong correlations between the two (PRL, r = 0.92; GH, r = 0.79). The lactogenic hormones were also determined together by the Nb2 cell bioassay (BA) in 38 of these same women, and the results compared with the sum of the PRL and GH immunoassays. There was a strong correlation between the BA and RIA (r = 0.75), and the BA/PRL+GH RIA ratio averaged 1.6 +/- 0.5. Corresponding values for IRMA were r = 0.66, and BA/PRL + GH IRMA 3.3 +/- 1.1. Thus, the polyclonal RIA antisera appeared to recognize bioactive hormone components not determined by the double monoclonal antibody IRMA. Another 23 women at risk for familial breast cancer, and 14 cystic breast disease patients were also studied. High BA, but normal RIA results, giving mean ratios of 2.4 +/- 1.1 and 3.6 +/- 3.0 respectively, suggest the presence of a further variant with high bioactivity not detected by RIA in these two clinical situations.
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PMID:Serum prolactin and growth hormone determined by radioimmunoassay and a two-site immunoradiometric assay: comparison with the Nb2 cell bioassay. 337 57

The estrogen receptor (ER)-positive human breast cancer cell line T 47D exhibited genetic instability under cell culture conditions which maintained almost continuous exponential growth. This resulted in the spontaneous generation of three ER-positive sublines with a range of DNA ploidies and distinctive phenotypes. One of these sublines, T 47D-5, exhibited resistance to the growth-inhibitory effects of the synthetic nonsteroidal antiestrogen tamoxifen and the synthetic progestin ORG 2058, in marked contrast to "wild type" T 47D cells (designated T 47D-7 in this study). T 47D-5 cells were cloned by limiting dilution and 11 clonal cell lines were tested for sensitivity to tamoxifen. Although all clones of T 47D-5 were significantly less sensitive than T 47D-7 cells, a spectrum of sensitivities was observed. Three clones, T 47D-5-13, T 47D-5-21, and T 47D-5-23, were further characterized by measuring the concentrations of receptors for estrogen, progesterone, growth hormone, and epidermal growth factor and responses to estradiol, tamoxifen, and progestin, in terms of both induction of specific proteins and effects on cellular proliferation. Although the T 47D-5 subline and clone T 47D-5-23 were insensitive to both the growth-stimulatory effects of estradiol and the inhibitory effects of tamoxifen, this was not related to the concentration of ER or its ability to induce progesterone receptor. Estrogen receptor levels were similar in resistant and sensitive clones of T 47D-5 [70,000-81,000 sites/cell] and were 2.5-fold greater than in the sensitive T 47D-7 line [32,600 +/- 5,000 (SEM) sites/cell]. Northern blots showed no difference in the size of ER mRNA transcripts between sensitive and resistant clones. Estradiol treatment increased progesterone receptor (PR) levels in all cell lines but the magnitude and sensitivity of this response were unrelated to growth responses indicating a divergence in estrogenic control of cellular proliferation and specific protein synthesis within these clones. T 47D-5, T 47D-5-13, T 47D-5-21, and T 47D-5-23 were all insensitive to the growth-inhibitory effects of ORG 2058. The progestin was also unable to increase lactogenic and epidermal growth factor receptor concentrations in these four lines in contrast to the response in T 47D-7 cells. The insensitivity to progestin in the T 47D-5 subline and its three clonal cell lines could be accounted for, in part, by a 75-80% reduction in PR levels when compared with T 47D-7 cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Genetic instability and the development of steroid hormone insensitivity in cultured T 47D human breast cancer cells. 339 Aug 30

For investigation of the bioactivity of circulating prolactin and growth hormone (lactogenic hormones) in symptomatic benign breast disease, serum was assayed by the Nb2 lymphoma cell method in premenopausal patients with cystic breast disease and cyclic mastalgia and in normal premenopausal women. The results were compared with serum prolactin and growth hormone concentrations determined by radioimmunoassay. The serum bioassayable hormone levels in the benign breast disease patients (74.0 +/- 77.6 ng/ml) were significantly higher (P less than .001) than in normal women (23.8 +/- 10.7 ng/ml). There were no significant differences in the radioimmunoassayable prolactin or growth hormone levels between the 2 groups. When 16 cystic breast disease patients were placed on a low-fat (20% of total kilocalories) diet for 3 months, there were significant reductions in the serum bioassayable hormone levels (P less than .02). It is concluded that the bioactivity of prolactin may be elevated in the serum of patients with cystic breast disease and cyclic mastalgia, without corresponding increases in levels determined by radioimmunoassay; that this abnormality is reversible by a reduction in dietary fat consumption to 20% of the total kilocalories; and that serum prolactin may provide a valuable biomarker in clinical trials of a low-fat diet in women at high breast cancer risk.
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PMID:Effect of a low-fat diet on hormone levels in women with cystic breast disease. II. Serum radioimmunoassayable prolactin and growth hormone and bioactive lactogenic hormones. 347 May 39

MCF-7 human breast cancer cells, grown in long-term tissue culture, were found to be highly responsive to prolactin in terms of growth even in the presence of serum. Human prolactin, placental lactogen, and growth hormone (50-250 ng/ml) stimulated MCF-7 cells to grow when added to culture medium of cells in the presence of charcoal-stripped serum. Within 3 days of the hormone addition, a 4.4-fold increase in cell number was achieved with human prolactin at 100 ng/ml in the presence of 10% charcoal-stripped serum. Under these same conditions, estradiol-17 beta at 10(-8) M achieved only a 2-fold increase. After 6 days of culture, both estradiol-17 beta and prolactin gave a total 5-fold increase in cell number. No prolactin effect was achieved in the presence of 10% fetal bovine serum. Stripping fetal bovine serum with dextran-coated charcoal removes as much as 85% of the endogenous lactogens. Removal of these hormones is essential for demonstration of subsequent prolactin-induced growth response in MCF-7 cells, since bovine prolactin binds effectively to lactogen receptors on the surface of the cells but does not transmit a growth signal. When added simultaneously with human prolactin, bovine prolactin blocks the growth response to the former hormone. These results clearly demonstrate that, under the proper conditions of culture, the human breast cancer cell line MCF-7 is highly responsive to growth stimulation by homologous lactogenic hormones. This then affords us an excellent model for further studies on the possible role of prolactin in growth and maintenance of human breast cancer.
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PMID:Role of serum in the prolactin responsiveness of MCF-7 human breast cancer cells in long-term tissue culture. 358 Oct 86

We have initiated an analysis of the action of prolactin in a human breast cancer cell line (T-47D) by isolating and sequencing cDNA clones for a prolactin-inducible protein (PIP). PIP cDNA (approximately 600 base pairs) was isolated from a lambda gt11 expression library prepared from mRNA extracted from T-47D cells treated with prolactin and hydrocortisone. The identity of PIP cDNA was confirmed by hybrid-selected translation. PIP mRNA is a single mRNA species of approximately 900 bases which responds to lactogenic hormones (human prolactin and growth hormone) in a time- and dose-dependent manner. Treatment of T-47D cells with human growth hormone (hGH) increased PIP mRNA levels by 4.6-fold, while the combination of hGH and hydrocortisone or dihydrotestosterone had a more dramatic, 12.4-fold, effect. The latter steroid was the most potent. Dihydrotestosterone plus hGH increased transcription of the PIP gene by 3.7-fold. Dihydrotestosterone alone was as effective as dihydrotestosterone plus hGH in increasing the transcription rate, while hGH alone had no effect. Thus, lactogen may regulate PIP gene expression at a post-transcriptional step. PIP mRNA was expressed at low levels in other human breast cancer cell lines which were prolactin receptor-positive; MCF-7 and EFM-19 lines were exceptions. PIP cDNA had an open reading frame of 146 amino acids, sufficient to encode the precursor form of the secreted PIP protein (approximately 14.5 kDa). The similarity of the predicted amino acid sequence of PIP to the sequence of a protein encoded by a gene expressed in the mouse submaxillary gland prompted us to look for PIP in human saliva. Western blot analysis confirmed the presence of PIP in human saliva. Therefore, the PIP gene is useful in studying the molecular actions of the prolactin/growth hormone polypeptide hormone family and the interaction with androgen, in mammary and other potential target cells.
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PMID:Isolation and sequencing of a cDNA clone for a prolactin-inducible protein (PIP). Regulation of PIP gene expression in the human breast cancer cell line, T-47D. 366 31

The fact that pregnancy lowers long-term basal prolactin secretion has lead to the suggestion that low prolactin levels, which by inference may occur after pregnancy at an early age, may protect against breast cancer. There is evidence that prolactin is a co-carcinogen in rodent mammary cancer, but aspects of rodent mammary gland biology may not be applicable to humans. Research in primates suggests that some factor from the pituitary is required for breast cancer, although it is neither prolactin nor growth hormone. similarly, one experiment has been reported that some pituitary factor may potentiate estrogen in promoting growth of human breast cancer cells in cell culture. Treatment of human breast cancer with prolactin-lowering drugs, however, is ineffective. Removal of the pituitary os effective in treating human breast cancer, and furthermore, persons without mature breast tissue, such as women with Turner's syndrome or men, have a very low incidence of breast cancer. Overall, the evidence linking prolactin to breast cancer is insufficient to warrant use of prolactin-lowering ergot drugs as a preventive measure in those at risk of breast cancer.
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PMID:Prolactin and breast cancer. 379 3

Estrogen, prolactin, and other tissue-derived factors are implicated in the etiology and pathophysiology of human breast cancer (HBC). In a previous study, we demonstrated that a factor(s) secreted by rat pituitary tumor cells (GH3) synergizes with estrogen to induce growth of HBC cells (T-47D) transplanted into athymic nude mice. The present studies were carried out to characterize further this pituitary growth factor. Pituitary tumor cell lines (GH3, GH1, 235-1, and AtT-20) and normal rat pituitaries were transplanted s.c. into estrogen-treated (estradiol valerate injection, 500 micrograms/14 days) athymic nude mice which also received T-47D cells. The influence of the presence of these normal and tumorous pituitary cells on growth (size and weight) of T-47D tumors was monitored for 49 to 56 days. The results indicate that factor(s) from normal rat pituitary glands as well as from the GH1 and GH3 but not 235-1 and AtT-20 pituitary tumor cells were able to potentiate the growth of T-47D tumors in estrogenized mice. To ascertain whether or not prolactin and/or growth hormone are responsible for the growth-promoting activity, purified human and ovine growth hormone and ovine prolactin were administered to estrogenized athymic nude mice either by daily s.c. injection (100 micrograms/day) or by constant infusion using Alzat osmotic minipumps (1.25 and 5.0 micrograms/h) for 29 to 56 days. None of these treatments stimulated the growth of the T-47D tumors, suggesting that prolactin, growth hormone, and their intermediates may not be directly involved. We further determined whether the factor from pituitary tumor cells was present in serum-free conditioned medium and could stimulate the growth of HBC cells in vitro. Conditioned medium from GH3 and GH1 but not from 235-1 and AtT-20 pituitary cells significantly stimulated growth of T-47D cells in the presence of estradiol (10(-10) M) after 12 days of culture in a serum-free medium (Dulbecco's modified Eagle's medium containing bovine serum albumin, 0.5 mg/ml). Optimal serum-free growth of T-47D cells (2-fold above control) was observed in the presence of estradiol (10(-10) M) and conditioned medium (30% v/v) from 48-h cultures of GH3 cells. The bovine serum albumin concentration of the serum-free medium (Dulbecco's modified Eagle's medium) was also important: optimal T-47D cell proliferation was observed with BSA between 0.5 and 2.0 mg/ml. Conditioned medium preparations from serum-pretreated flasks (without cells) from GH3 cell monolayers for zero time and from actinomycin D plus cycloheximide-inhibited GH3 cells were inactive.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Evidence for a novel pituitary factor that potentiates the mitogenic effect of estrogen in human breast cancer cells. 400 46

The concentrations of growth hormone (GH) and prolactin (PRL) in the serum of 42 breast cancer patients were determined by radioimmunoassay (RIA). Forty percent of the patients had elevated GH levels while only 17% had elevated PRL levels. These findings suggest a relationship between GH and breast cancer; a weaker correlation exists between PRL and this malignancy. In addition, total lactogens in the serum were measured by a bioassay (BA). The BA/RIA (GH + PRL) ratio was greater in the breast cancer patients than the controls, indicating that variant forms of the hormones with higher than normal biological activity might be present.
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PMID:Elevated growth hormone levels in sera from breast cancer patients. 405 32

Postmenopausal patients with metastatic breast cancer were treated with medroxyprogesterone acetate (MPA) (Clinovir) in dosages between 500 and 1500 mg orally per day. The relation of MPA plasma concentrations and endocrine effects were studied in a longitudinal fashion. MPA exerted suppressive effects on the basal and gonadotropin-releasing hormone (GnRH) stimulated gonadotropin secretion, cortisol, dehydroepiandrosterone (DHEA), and estradiol (E2) in a dose-dependent manner leading to a complete suppression with 1500 mg orally per day. The depression of thyroid hormones (T3 and T4) coincided with a depression of the thyroxine-binding index (TBI). MPA did not affect human growth hormone (hGH), basal and thyrotropin-releasing hormone (TRH) stimulated thyroid-stimulating hormone (TSH) and aldosterone. Basal and TRH-stimulated prolactin (PRL) secretion showed a slight but distinct elevation. From these data it is concluded that in postmenopausal patients MPA exerts its antitumor activity by an interference with the hypothalamo-pituitary adrenal axis in the sense of a selective pharmacologic hypophysectomy leading to complete suppression of adrenal steroid secretion. Additionally, MPA inhibits tumor cell growth through the progesterone receptor. A dual mechanism for the antitumor activity of high dose is postulated MPA: ablative through suppression of the hypothalamo-pituitary-adrenal axis and subsequent estrogen deprivation, and additive via the progesterone receptor directly on the tumor cell. The significance of gonadotropin suppression in the postmenopause for breast cancer growth is unclear. The depression of T3 and T4 is due to a depression of thyroid hormone-binding proteins. The elevation of PRL secretion may be explained by a slight estrogenic activity of MPA metabolites.
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PMID:Pharmacokinetic and pharmacodynamic basis for the treatment of metastatic breast cancer with high-dose medroxyprogesterone acetate. 608 20


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