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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The estrogen receptor binding, and growth suppressant and stimulating effects in MCF-7 human breast cancer cells, of four structural variants of the triarylethylene antiestrogen tamoxifen (1) were studied. In these analogs, the dialkylaminoethoxy side chain of 1 was replaced by carboxylic acid or oxyacetic acid substituents. The presence of a p-hydroxy group in the ring geminal to the one bearing the side chain resulted in ligands with estrogen receptor affinities greater than that of 1 but less than that of estradiol. Compared to 1, none of the test compounds were effective suppressants of cell growth. To the contrary, the phenolic oxyacetic acid analog effectively reversed the growth suppressive effect of 1. Also, it was as effective as estradiol, though less potent, in stimulating growth of cells grown in estrogen depleted medium, suggestive of full estrogen agonist activity. Its carboxylic acid counterpart had little or no effect on proliferation. Because the phenolic oxyacetic acid is a metabolite of 1 in animals, its estrogenicity may have therapeutic implications of concern, depending on the extent to which it is formed and distributed in tissues of patients receiving 1.
J Steroid Biochem Mol Biol 1992 Jul
PMID:Estrogen receptor affinity and effects on MCF-7 cell growth of triarylethylene carboxylic acids related to tamoxifen. 163 24

Within the framework of experiments related to the association between dietary fiber and breast cancer an in vitro test system was used to study the binding of estrogens to various fibers (e.g. cholestyramin, lignin and cellulose) and fiber sources (e.g. wheat bran, cereals, seeds and legumes). Furthermore, the in vivo apparent digestibility of the different fiber sources was tested using a mobile nylon bag technique in intestine-cannulated pigs. Estradiol-17 beta (E2) bound more strongly to the various fibers than did estrone (E1), estriol or estrone-3-glucuronide. At increasing pH (greater than 7) binding of both E1 and E2 to wheat bran decreased significantly. Cholestyramine and lignin bound almost all estrogens present in the medium. Linseed (91%), oats (83%), barley chaff (88%) and wheat bran (82%) are other excellent binders of E2. Corn, rye and white wheat flour showed lower binding capacity with a relatively low affinity. Cereals with the highest percentage of lignin in the fiber (greater than 3%) were also the fiber sources with the lowest apparent digestibility. Estrogens bound with the highest affinity (relative to bovine serum albumin) to these fiber sources. Together with wheat bran and lignin, oats, linseed and soybean seem to be products with good perspectives for in vivo evaluation of the lowering effect of dietary fiber on estrogen exposure of estrogen-sensitive tissues.
J Steroid Biochem Mol Biol 1991 May
PMID:In vitro binding of estrogens by dietary fiber and the in vivo apparent digestibility tested in pigs. 164 89

Insulin-like growth factor-I (IGF-I) receptors are present in breast cancer cells and may play a role in breast cancer cell growth. We have studied the effect of progestins on IGF-I receptors in T47D human breast cancer cells. T47D cells constitutively express high levels of progesterone receptors and are a model for studying the regulation of cellular functions by progestins. Treatment of T47D cells with either progesterone or the synthetic progestin promegestone (R5020) decreased IGF-I receptor content by approximately 50%, as measured by Scatchard analysis and receptor biosynthesis studies. In contrast to progestins, estradiol, dexamethasone, and dihydrotestosterone did not influence IGF-I receptor content. No effect of R5020 was seen after 12 h of incubation, a near-maximal effect was seen after 24 h, and greatest effects were seen after 72 h. R5020 decreased IGF-I receptor mRNA abundance, indicating that progestins acted at the level of gene expression. However, progestins also increased the secretion of IGF-II, a ligand for the IGF-I receptor. In contrast to IGF-II, T47D cells did not express IGF-I. The addition of exogenous IGF-II to T47D cells down-regulated both IGF-I receptor binding and IGF-I receptor mRNA abundance. This study indicates, therefore, that progestins regulate IGF-I receptors in breast cancer cells and suggests that this regulation occurs via an autocrine pathway involving enhanced IGF-II secretion.
Mol Endocrinol 1991 May
PMID:Progestins induce down-regulation of insulin-like growth factor-I (IGF-I) receptors in human breast cancer cells: potential autocrine role of IGF-II. 164 93

Although retinoic acid has been shown to inhibit proliferation in human breast cancer cells, the mechanisms by which these effects are mediated are not known. Since several steroid hormones and their synthetic antagonists also inhibit proliferation of human breast cancer cells, we investigated the interactions between retinoic acid, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] and antioestrogens in the control of human breast cancer cell proliferation in vitro. When T-47D cells, the most sensitive of six human breast cancer cell lines to the growth inhibitory effects of retinoic acid, were treated with retinoic acid and 1,25-(OH)2D3, a synergistic inhibitory effect on cell growth was observed. Retinoic acid also enhanced the growth inhibitory effect of various antioestrogens (4-hydroxytamoxifen, 4-hydroxyclomiphene or LY117018). However, retinoic acid did not affect oestradiol-induced growth stimulation. Measurement of the cellular receptors for 1,25-(OH)2D3 and oestrogen revealed no significant change in receptor levels following treatment with concentrations of retinoic acid which modulated growth. These results indicate that retinoic acid not only has direct growth inhibitory effects on breast cancer cell proliferation but also augments the effects of some other known regulators of breast cancer cell replication including 1,25-(OH)2D3 and antioestrogens. Synergism appears to involve interactions with steroid hormone action distinct from changes in steroid hormone receptor levels.
J Steroid Biochem Mol Biol 1991 Oct
PMID:Retinoic acid acts synergistically with 1,25-dihydroxyvitamin D3 or antioestrogen to inhibit T-47D human breast cancer cell proliferation. 165 97

We have studied the regulation by estradiol of the mannose-6-phosphate (Man-6-P)/insulin-like growth factor-II (IGF-II) receptor concentration in different breast cancer cell lines. The mRNA level was assayed by Northern blot using the H5.1 cDNA probe. The protein level was assayed by Western ligand blot, by binding saturation with [125I]procathepsin-D on total membrane preparations, and by immunoprecipitation of 35S-labeled proteins. In three estrogen receptor-positive cell lines (MCF7, T47D, and ZR75-1), estradiol specifically decreased the steady state level of the Man-6-P/IGF-II receptor protein and mRNA. Moreover, in different cell lines and in primary culture of normal mammary cells, the secretion of procathepsin-D was inversely correlated with the level of Man-6-P/IGF-II receptor protein and mRNA. We conclude that estradiol down-regulates the Man-6-P/IGF-II receptor in breast cancer cells. Since two of its ligands, procathepsin-D and IGF-II, are induced by estrogen, we propose that the Man-6-P/IGF-II receptor becomes saturated after estrogen treatment. This model might explain the previously described estrogen-induced secretion of procathepsin-D and other lysosomal proenzymes routed by the same transport system.
Mol Endocrinol 1991 Jun
PMID:Estradiol down-regulates the mannose-6-phosphate/insulin-like growth factor-II receptor gene and induces cathepsin-D in breast cancer cells: a receptor saturation mechanism to increase the secretion of lysosomal proenzymes. 165 43

A dispersed guinea pig adrenal system has been used to study the effect of the aromatase inhibitor rogletimide (RGL) on adrenal steroidogenesis. The ACTH-stimulated release of cortisol, 17-hydroxyprogesterone (17-OHP) and androstenedione (A) was measured following exposure of adrenal cells to RGL, or the other aromatase inhibitors aminoglutethimide (AG) and CGS 16949A. RGL at concentrations sufficient to cause 80-90% inhibition of placental microsomal aromatase had no effect on the release of all three steroids. In contrast, AG at 10(-5) M markedly reduced the output of all three steroids from these cells. CGS 16949A at 10(-6) M reduced the output of cortisol and increased the concentration of 17-OHP and A. These results indicate that RGL is unlikely to cause the suppression of cortisol synthesis which has been noted to occur with AG and CGS 16949A during the treatment of breast cancer patients.
J Steroid Biochem Mol Biol 1991 Nov
PMID:The effect of the aromatase inhibitor, rogletimide (pyridoglutethimide), on guinea pig adrenal cell steroidogenesis and placental microsomal aromatase activity: comparison with aminoglutethimide and CGS 16949A. 165 68

Studies on estrogen receptor (ER)-positive human breast cancer cell lines have shown that estrogen treatment positively modulates the expression of the genes encoding transforming growth factor-alpha (TGF alpha), 52-kDa cathepsin-D, and pS2. To determine whether these genes would be similarly regulated by estrogens in normal human mammary epithelial cells, we stably transfected immortal nontumorigenic human mammary epithelial cells with an ER-encoding expression vector. ER-negative tumor cells were also transfected for comparison. Levels of TGF alpha and 52-kDa cathepsin-D mRNA were enhanced by estrogen treatment of both ER-transfected immortal and tumorigenic cells, demonstrating that the ER by itself is sufficient to elicit estrogenic regulation of the expression of these genes. In contrast, expression of the pS2 gene was detected only in the ER-transfected tumor cells. The ER in both cell lines is capable of recognizing the pS2 promoter, however, since estrogen enhanced the activity of an introduced pS2-CAT reporter plasmid in transient expression analyses. These and other experiments with somatic cell hybrids between the immortal cells and ER+/pS2+ MCF-7 tumor cells, where pS2 gene expression is extinguished, support the conclusion that the immortal nontumorigenic cells encode gene products that block endogenous pS2 expression. These results also imply that such repressors are not active in the tumor cells.
Mol Endocrinol 1991 Nov
PMID:Induction of estrogen-regulated genes differs in immortal and tumorigenic human mammary epithelial cells expressing a recombinant estrogen receptor. 166 44

Cytogenetic, flow cytometric, cytophotometric and morphometric analyses were performed on 22 previously untreated, primary solid breast carcinomas. Although the cell nuclei as the primary object of these studies were the same in all the tumors, distinct features were evaluated in each case to determine to what degree the results obtained by these techniques are comparable. From the cytogenetic viewpoint, six tumors had a modal number in the diploid range, seven were in the triploid range, and two in the tetraploid range; seven tumors had no modal number. These data correlate with the flow cytometry and cytophotometry results obtained, with DNA values slightly higher than their respective chromosomal modes. However, no correspondence between chromosomal modes and mean nuclear area was found. Chromosomal markers have been identified that particularly affect chromosomes 1 (p11, q21-qter), 11 and 16, although no common markers existed in all cases. Cytogenetics is the most sensitive technique, but the low yield (22 out of 140 tumors assayed) considerably restricts its value in any prospective breast cancer study.
Virchows Arch B Cell Pathol Incl Mol Pathol 1991
PMID:Cytogenetics, flow cytometry, cytophotometry and morphometry of 22 cases of primary breast carcinoma. A comparative study. 168 21

Inositol lipid hydrolysis was monitored in the human breast cancer cell line MCF-7 in response to various bombesin (BN) and substance P (SP) analogues. Both members of the BN family of peptides, i.e. BN and gastrin-releasing peptide (GRP), stimulated a dose-related increase in total inositol phosphate production, with a similar half-maximal effective dose (ED50) around 1 nM. The BN receptor antagonist [Leu13-psi-CH2NH-Leu14]-BN (LLBN) at 1 microM was devoid of agonist activity and displaced the BN dose-response to the right, resulting in a tenfold increase in the ED50 for BN. BN also stimulated a dose-related increase in 45Ca2+ efflux which was also inhibited by LLBN. Two SP analogues [DArg1,D-Pro2,D-Trp7,9,Leu11]-SP and [D-Arg1,D-Phe5,D-Trp7,9,Leu11]-SP ([APheTL]-SP), both antagonized BN-stimulated inositol lipid hydrolysis. [APheTL]-SP (60 and 80 microM) alone also exhibited considerable agonist activity which was not antagonized by LLBN. Indeed, a sub-threshold dose of [APheTL]-SP (40 microM) in the presence of LLBN (10 microM) potentiated the inositol lipid hydrolysis response. BN, GRP, LLBN and [APheTL]-SP all inhibited binding of 125I-labelled GRP to MCF-7 cells, to 50% of that occurring in the absence of the peptides, at concentrations of 150 pM, 150 pM, 150 nM and 600 nM respectively. These data are consistent with the presence of separate but interacting receptors or binding sites for BN and SP analogues, which are coupled to a common signal transduction pathway in human breast cancer cells.
J Mol Endocrinol 1991 Feb
PMID:Modulation of inositol lipid hydrolysis in human breast cancer cells by two classes of bombesin antagonist. 170 28

BCA200 has been described as a 200,000 Mr monomeric cell surface glycoprotein associated with human breast cancer. Since the physical properties and cellular distribution of BCA200 resemble those of c-erbB-2, antibodies to BCA200 were tested for the ability to bind a recombinant protein containing the c-erbB-2 extracellular domain (erbB-2 ECD). Three antibodies to distinct epitopes of BCA200 reacted with erbB-2 ECD but not with a control protein expressed in a similar baculovirus lysate. Control myeloma proteins and antibodies to four other antigens did not react with erbB-2 ECD. A protein with the expected molecular weight for erbB-2 ECD was also immunoprecipitated by anti-BCA200 antibody 520C9. We conclude that BCA200 is another synonym for c-erbB-2.
Mol Immunol 1991 Aug
PMID:Identity of BCA200 and c-erbB-2 indicated by reactivity of monoclonal antibodies with recombinant c-erbB-2. 171 33


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