Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Conventionally in vitro cytotoxicity assays are performed as single-end-point determinations. To compensate for the diversity of growth rates among different cell lines in this report we describe a computerized kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. As a prerequisite four human breast cancer cell lines (MDA-MB-231, MCF-7, T-47-D and ZR-75-1) were characterized with regard to oestrogen and progesterone receptor content, modal chromosome number and proliferation kinetics depending on the number of passages in culture. With prolonged time in culture for ZR-75-1 exposed to various concentrations of cisplatinum a dose-related increase in drug effect was observed. Owing to a correction of the T/C values for the initial cell mass (at the time when drug is added) a sharp distinction between cytostatic and cytocidal drug effects becomes obvious in plots of corrected T/C values versus time of incubation. The influence of the untreated control on the corrected T/C values and possible time courses of theoretical inhibition profiles (reflecting cytostatic, transient cytotoxic or cytocidal drug effects as well as development of resistance) and their relationship to the corresponding growth curves of drug-treated cells are discussed. Chemosensitivity assays with diethylstilbestrol dipropionate, tamoxifen, melphalan, cisplatinum, vinblastine, Adriamycin and 5-fluorouracil prove the theoretical considerations to be true for MDA-MB-231, MCF-7, T-47-D and ZR-75-1 human breast cancer cell lines in practice.
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PMID:Standardized kinetic microassay to quantify differential chemosensitivity on the basis of proliferative activity. 130 32

The effect of hyaluronidase and a combination of hyaluronidase with Adriamycin was investigated on several breast cancer models in vitro and in vivo. In vitro enzyme treatment (using concentrations up to 80,000 IU/1) of murine (MXT-, MXT +/-, and MXT+) and human (MCF-7, ZR-75-1 and T-47-D) breast cancer cell lines did not inhibit tumour cell proliferation (measured by a kinetic crystal violet assay) in either case. Although high-dose hyaluronidase (1.2 x 10(6) IU/kg) was ineffective, when administered peritumourally to the MXT M3.2 mammary carcinoma of the B6D2F1 mouse, it is remarkable that five "megadoses" were excellently tolerated. However, the antineoplastic activity of Adriamycin against the oestrogen-receptor-positive variant of the MXT tumour was significantly enhanced by combination with concentrations of hyaluronidase that were inactive per se, both in vitro and in vivo. Interestingly, the enhancement of the in vivo antitumour activity was not compromised by toxic side-effects.
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PMID:Hyaluronidase enhances the activity of adriamycin in breast cancer models in vitro and in vivo. 151 81

The mitochondrial ATPase inhibitor proteins--the Pullman-Monroy inhibitor (PMI) and the Ca(2+)-binding protein (CaBI)--have a wide distribution, both being present in mitochondria of bovine heart and kidney, rat liver and brain, two mitochondrial populations of rabbit skeletal muscle, and mitochondria from human fibroblasts and the human breast cancer cell line T-47-D. The ratio of CaBI to PMI was highest in heart and skeletal muscle mitochondria. The subsarcolemmal fraction of skeletal muscle had 2.6-times as much CaBI as did the intermyofibrillar. The ratio of CaBI to PMI in the mitochondria of the other normal tissues and fibroblasts was close to 1. In contrast, mitochondria from T-47D cells had 1.5-times as much PMI as CaBI whilst mitochondria from fibroblasts from a patient with Luft's disease showed a virtual lack of PMI. The specific ATPase, ATP-synthetase and succinate dehydrogenase activities of the Luft's mitochondria were, however, in the normal range. The specific ATP synthetase activity of the T-47D cells was significantly higher than normal. We conclude that tissues like heart and skeletal muscle which experience wide fluctuations in intracellular Ca2+ have a greater need for CaBI. Why lack of PMI could lead to 'loose' coupling of oxidative phosphorylation in skeletal muscle of Luft's patients, but not in fibroblasts is discussed.
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PMID:Distribution of the ATPase inhibitor proteins of mitochondria in mammalian tissues including fibroblasts from a patient with Luft's disease. 153 26

Breast self-examination (BSE) and medical breast examination practices were studied in a group of 1,103 women without diagnosed breast cancer, randomly sampled to conform in age and social status with breast cancer cases from the population of Brisbane, Australia between 1981 and 1985. Relationships between these practices and sociodemographic factors, breast cancer risk indicators, health related behaviors and source of knowledge about BSE were analyzed. Overall, 63% of women reported performing BSE. BSE was practiced frequently (monthly or more). BSE frequency was only weakly associated with breast cancer risk indicators. It was more strongly linked with age, the 20-44 year group being more likely to examine their breasts occasionally and the women 65 years and over being less likely to examine their breasts. Married women were the most likely to practice BSE frequently and widowed or single women most likely never to practice. Women who underwent cervical smear testing were more likely to perform BSE than those who did not have smear tests. Women who learned BSE from their doctors as opposed to other sources practiced BSE more frequently and were more likely to practice BSE exactly as taught.
Asia Pac J Public Health 1991
PMID:A profile of Australian women practicing breast self-examination. 184 20

When deprived of steroid in the long term, T-47-D human breast cancer cells lose estrogen sensitivity of cell growth. This loss of response results from an increased basal growth rate in the absence of steroid, not from a loss of estrogen-stimulated growth, and it occurs without any loss of estrogen receptor number or function. Growth factor gene expression and sensitivity have been investigated in this model system in an attempt to unravel the molecular mechanisms underlying the progression to steroid autonomy. The transition was accompanied by a decreased dependence on added serum and by a loss of the stimulatory effects of insulin and basic fibroblast growth factor, but also by an acquired sensitivity to stimulation by transforming growth factor-beta (TGF-beta). An increase in TGF-beta 1 mRNA was detected following loss of steroid sensitivity. There was no increase in epidermal growth factor (EGF) receptor number. These findings are discussed in relation to current knowledge concerning the mechanisms by which estrogens stimulate breast cancer cell proliferation.
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PMID:Interaction of growth factors during progression towards steroid independence in T-47-D human breast cancer cells. 219 68

An in vitro model system is described for studying the problem of loss of steroid sensitivity in breast cancer cells. Growth of cloned oestrogen-sensitive human breast cancer cells in the long-term absence of steroid gives rise to a population of oestrogen-insensitive cells. In ZR-75-1 cells, the effect is clonal but occurs at high frequency suggesting a mechanism affecting a wide proportion of the cell population synchronously. This does not involve any reduction in oestrogen receptor number. Furthermore, there is no coordinated loss of oestrogen-sensitive molecular markers, showing that oestrogen receptors remain not only present but functional. These growth changes are not accompanied by any loss of growth inhibition by antioestrogen. Although steroid deprivation does not result in loss of oestrogen-sensitive markers, this does not hold true for other steroids. There was a reduction in progestin, androgen and glucocorticoid regulation on transfected LTRs. Loss of steroid-sensitive growth was accompanied by changes in response to exogenous growth factors and altered endogenous growth factor mRNA production. Steroid-deprived T-47-D cells acquire sensitivity to stimulation by TGF beta and have raised TGF beta 1 and TGF beta 2 mRNA levels. ZR-75-1 cells are growth inhibited by TGF beta and have reduced TGF beta 1 mRNA levels. In MCF-7 cells, increased IGFII mRNA, following transfection, can result in an increased basal cell growth rate in the absence of steroid. These findings are discussed in relation to possible autocrine mechanisms in the loss of steroid sensitivity of breast cancer cells.
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PMID:Transition of human breast cancer cells from an oestrogen responsive to unresponsive state. 228 87

When deprived of steroid in the long term, both estrogen-dependent (ZR-75-1) and estrogen-responsive (T-47-D) human breast cancer cells lose estrogen regulation of cell growth in a reproducible time course using both stock lines and recloned cells. The estrogen-stimulated growth rate was unaffected by such treatment, but there was an increase in the basal growth rate without steroid. For ZR-75-1 cells, the effects are clonal but occur at high frequency (1 in 1000 cells) and synchronously between clones, suggesting a phenotypic mechanism. These changes in cell growth occur without any coordinated loss of estrogen sensitivity of molecular markers (pS2 mRNA, progesterone receptor protein) showing that functional estrogen receptors remain present throughout. The constitutive expression of progesterone receptor in one clone of steroid-deprived ZR-75-1 cells does suggest, however, that alterations in expression of individual estrogen-sensitive genes can occur. Loss of estrogen-stimulated growth was not accompanied by loss of growth inhibition by antiestrogen, and the latter effect remained reversible by estradiol. In an attempt to understand the molecular mechanisms underlying the loss of steroid sensitivity in the two cell lines, growth factor gene expression was investigated. Progression to steroid autonomy in T-47-D cells was accompanied by an upregulation of transforming growth factor (TGF) alpha, TGF beta 1, and TGF beta 2 mRNA. However, TGF beta 1 mRNA was downregulated in two ZR-75-1 steroid-deprived clones. These findings are discussed in relation to possible autocrine mechanisms in the loss of steroid sensitivity of breast cancer cells.
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PMID:Cellular and molecular events in loss of estrogen sensitivity in ZR-75-1 and T-47-D human breast cancer cells. 239 57

Multihormonal regulation on the long terminal repeat (LTR) region of mouse mammary tumour virus (MMTV) has been studied using T-47-D human breast cancer cells stably transfected with the steroid sensitive LTR-C3 chimaeric gene. The specificity of steroid action on transfected LTR sequences has been compared with regulation of endogenous cellular markers. We conclude that the hormone response element of the LTR can be induced by physiological concentrations of androgen, progestin and glucocorticoid. 17 beta-Oestradiol did not regulate the LTR at physiological levels but an effect was found at 10(-6) M. This effect was not inhibited by antioestrogen nor was it reproduced by the synthetic oestrogen diethylstilboestrol suggesting such effects do not occur via the oestrogen receptor. The antioestrogens tamoxifen and transhydroxytamoxifen do not induce the LTR. No significant steroid competition was found in LTR regulation: whilst oestradiol did not act at physiological concentration it did not interfere with induction by androgen, progestin or glucocorticoid. Such gene regulation did not simply follow receptor status of the cells nor was it reflected in patterns of growth regulation by steroids. The implications of these findings on the mechanism of steroid hormone action are discussed.
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PMID:Multihormone regulation of MMTV-LTR in transfected T-47-D human breast cancer cells. 253 37

The influence of low- and high-density lipoproteins on the proliferation of human breast cancer cells in culture was studied. We compared total cell number after incubation for 48 hr in culture medium containing or lacking plasma lipoproteins. Marked differences were found between hormone-dependent (MCF-7, T-47-D, ZR-75) and hormone-independent (MDA-MB-231, HBL-100) mammary tumor cell lines. The cells also reacted differently on the different lipoproteins offered in the medium. Human low-density lipoproteins (LDL) exhibited a marked stimulation of the growth of hormone-independent cell lines but no or only toxic effects upon the hormone-sensitive lines. Human high-density lipoproteins (HDL) stimulated the proliferation of all cell lines in a dose-dependent manner but hormone-independent cells showed a higher response. These findings point towards different utilizations of nutrients in hormone-dependent and hormone-independent cells.
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PMID:Effects of low- and high-density lipoproteins on the proliferation of human breast cancer cells in vitro: differences between hormone-dependent and hormone-independent cell lines. 271 93

In order to improve the knowledge of prolactin receptors (PRL-R) in human breast tumors, we studied PRL-R modulation by lactogenic and steroid hormones in the PRL-R rich human breast cancer cell-line, T-47 D. The PRL-R were assayed on a preparation of cell total membranes. We demonstrated an abnormal homologous in vitro regulation of PRL-R. Concentrations of human growth hormone (hGH) greater than 500 ng/ml were required to cause a decrease in PRL-R, with a maximal down-regulation at 2000 ng/ml and for 48 hours. Human placental lactogen (hPL) induced a decrease in PRL-R at concentrations greater than 500 ng/ml but later than hGH; ovine prolactin (oPRL) had no effect on PRL-R. Moreover, we also demonstrated that progestins specifically modulated the expression of PRL-R in T-47D cells: Org 2058, a synthetic progestin induced a statistically significant increase in PRL-R after a twenty-four hour incubation period: this effect was already observed at 10(-9) M and was maximal for 10(-6) and 10(-5) M (186% +/- 3.5% (+/- SEM) for total PRL-R). At 10(-6) M, the stimulation occurred early at three hours and was maximal at twenty-four hours. Conversely estradiol (10(-9) to 10(-6) M), cortisol (10(-9) to 10(-6) M), dexamethasone (10(-9) to 10(-5) M) and RU 486 (10(-9) to 10(-5) M), a progestin and glucocorticoid antagonist, had no effect on PRL-R levels. The Org 2058 PRL-R stimulation was abolished in the presence of RU 486. The abnormal PRL-R down-regulation in the human breast cancer cell-line, T-47D, may contribute a growth advantage to these malignant cells over normal tissues. The progestin PRL-R dependence suggests that high levels of PRL-R may reflect a functional progesterone receptor (Pg-R) and a highly hormone-dependent-phenotype of the tumor. These results support a potential role of PRL in the etiology of breast tumors and may have important implications in the management of human breast cancer.
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PMID:Modulation of prolactin receptors (PRL-R) by lactogenic and steroid hormones in human breast cancer cells in long-term tissue culture (T-47D). 276 10


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