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

In earlier studies it has been shown that women with breast cancer and at risk for breast cancer have low excretion of urinary mammalian lignans (enterolactone and enterodiol) mainly due to low intake of whole-grain products and other fiber-rich foods. It is well known that estradiol (E2) has proliferative effects on estrogen dependent cancer cells and that antiestrogens inhibit this effect. To elucidate whether enterolactone (Enl) has antiestrogenic properties we studied, using MCF-7 breast cancer cells in culture, the in vitro effect of relatively low concentrations of Enl added both alone and in combination with E2. E2 (1 nmol/l) and Enl (0.5-2 mumol/l) separately stimulated the proliferation of MCF-7 cells, but their combination always resulted in lower stimulation than any of them alone, or the combined compounds had no stimulatory effect at all compared to the control. Higher concentrations above 10 mumol/l of Enl inhibited significantly the growth of the cells suggesting a toxic effect. The lignan was very rapidly conjugated to its monosulfate. It is suggested that one possible mechanism by which Enl may affect the growth of these estrogen sensitive cells is by competition of Enl and its sulfate with the estrogens for sulfokinases and sulfatases involved in estrogen metabolism in the cells. It is concluded that Enl inhibits E2-stimulated MCF-7 breast cancer cell growth in vitro, and vice versa. The concentrations of Enl needed for the elimination of the proliferative effect of E2 are physiologic and similar to those used in corresponding experiments utilizing tamoxifen.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Enterolactone and estradiol inhibit each other's proliferative effect on MCF-7 breast cancer cells in culture. 156 32

Peripheral aromatase activity was measured in 24 postmenopausal women suffering from advanced breast cancer. The % conversion of androstenedione to oestrone was then assessed for a significant correlation with age, weight, height, Quetelets index (weight/height2, Q.I.) and length of menopause. Serum oestradiol (E2) levels were measured in 22 of the subjects and compared with the same indices. There was no correlation between E2 or aromatase activity with the length of menopause (P = 0.3 and P = 0.5, respectively). In our data aromatase activity did not correlate with age (P greater than 0.5, n = 22). Serum E2 levels (P = 0.07, n = 20) expressed a negative correlation (i.e. decreased) with age. There was also a poor correlation between aromatase activity and weight of Quetelets index (P = 0.3, n = 20 for both). Serum E2 levels showed a statistically significant correlation with weight (P = 0.01, n = 21), but the relationship with Quetelets index just failed to attain statistical significance (P = 0.07, n = 20). In both cases the regression line was positive. When aromatase activity was correlated with serum E2 levels the regression line was positive but not statistically significant (P = 0.4, n = 22). The data indicate that aromatase activity is only one factor determining the differences in serum E2 levels between postmenopausal women.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Aromatase activity, serum oestradiol and their correlation with demographic indices. 156 52

Polymorphism of estrogen (ER) and progestin receptors (PR) was analyzed simultaneously using high performance hydrophobic interaction chromatography (HPHIC). HPHIC was used previously to characterize four ER isoforms [Hyder et al., J. Chromat. 397 (1987) 251] based on retention times on Synchropak propyl (100 x 6 mm) HPLC columns (Synchrom, Inc.). ER and PR were prepared from human breast cancer. ER was labeled with 3 nM of either [3H]estradiol-17 beta ([3H]E) or [125I]iodoestradiol-17 beta ([125I]E) while PR was associated with 5 nM of either [3H]R5020 ([3H]R) or [125I]iodovinylnortestosterone ([125I]V). ER was resolved by HPHIC into isoforms MI (Rt = 11 min), I(Rt = 16 min), and II (Rt = 24 min). Isoforms I and II each accounted for ca 45% of specific binding. PR separated into isoforms MI (Rt = 14 min) and I (Rt = 21 min, 80% of specific binding) when eluted with the same gradient used for ER chromatography. Upon inclusion of 10 mM molybdate ER resolved into isoforms MI and MII (Rt = 16 min) and PR into isoforms MI and I (here however isoform MI represented 80-95% of specific binding). Elution patterns were preserved with different batches of stationary phase suggesting the integrity of the isoform distribution. HPLC profiles of ER isoforms labeled with earlier [125I]E or [3H]E were identical as were PR isoform profiles labeled with either [3H]R or [125I]V. Pairs of 125I- and 3H-labeled ligands were used in either combination to monitor ER and PR profiles simultaneously. Isoforms analyzed in 50 biopsies gave reproducible retention times, however the ratio between I and II for ER and MI and I for PR varied. This method allows rapid, simultaneous monitoring of the chromatographic behavior of ER and PR isoforms or other associating proteins or nucleotides. One may now better elucidate their interrelationship as it relates to the hormone-response mechanism.
J Steroid Biochem Mol Biol 1992 Apr
PMID:Simultaneous identification of estrogen and progesterone receptors by HPLC using a double isotope assay. 156 80

Of the total number of breast cancers approx. 30-50% are hormone-dependent and estradiol is one of the main factors of cancerization. Consequently, the control of this hormone inside the cancer cell is of capital importance because it is well established that the inhibition of estradiol biosynthesis can have a positive effect on the evolution of the disease. The blockage of estradiol can be obtained by the action of anti-aromatases, anti-sulfatases, the control of the 17 beta-hydroxysteroid dehydrogenase activity or by the stimulation of the sulfotransferase which converted the estrogens in their sulfates. In breast cancer tissue estrone sulfate is quantitatively the most important source of estradiol. In the intact cell, estrone sulfatase activity is very intense in the hormone-dependent cell lines (e.g. MCF-7, T-47D) but very small activity is observed in the hormone-independent (e.g. MDA-MB-231, MDA-MB-436) cell lines. However, this activity became very strong after homogenization in the hormone-independent cells, suggesting the presence of repressive factor(s) for this enzyme or its sequestering in an inactive form, in the intact cells of these cell lines. In a series of previous studies it was found that in hormone-dependent cell lines different anti-estrogens: tamoxifen and derivatives, ICI 164,384, very significantly decrease the estradiol concentration originated from estrone sulfate, and recently it was observed that Decapeptyl (D-Trp6-gonadotropin-releasing hormone) in the presence of heparin can also decrease the conversion of estrone sulfate into estradiol. No significant effect was obtained in the presence of heparin or Decapeptyl alone. The estrone sulfatase activity can be inhibited by progesterone, the progestagen R-5020, and testosterone. In another series of recent studies the presence of very strong estrogen sulfotransferase activity has been shown in one breast cancer cell line, the MDA-MB-468. We can conclude that: (1) the control of estradiol concentration can be carried out in the breast cancer tissue itself; (2) estrone sulfate can play an important role in the bioavailability of estradiol in the breast cancer cell; and (3) as is the case for the aromatase, the control of: the estrogen sulfatase, estrogen sulfotransferase, and 17 beta-hydroxysteroid dehydrogenase can be new targets for therapeutic applications in breast cancer.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Recent data on estrogen sulfatases and sulfotransferases activities in human breast cancer. 158 Sep 21

A prospective, longitudinal study was performed to test the hypothesis that environmental factors (e.g., diet or cigarette smoking) modulate genetic damage caused by treatment for breast cancer and render these women more susceptible to developing second malignancies. A total of 107 women (49 with breast cancer, 52 with benign breast masses, and 6 normal women) were enrolled. This report describes initial studies at the time of enrollment and disease presentation. Mutant frequency at the hprt locus and cloning efficiency of peripheral blood lymphocytes did not differ significantly among the 3 groups. Mutant frequency increased with age, with a history of cigarette smoking, and with the number of years that current smokers used cigarettes. There was no correlation in women with benign masses between mutant frequency and the incidence of chromosome aberrations (28 women) or sister chromatid exchanges (23 women). A maternal history of breast cancer did not influence mutant frequency. There was no significant relationship between dietary intake of vitamins A, B12, C and E, folacin, selenium, calcium, caffeine, or multivitamin pills, and mutant frequency. Serum folate levels in the deficient range were associated (P = 0.02) with elevated mutant frequencies, whereas SCE rates inversely correlated with serum vitamin B12 levels. These results confirm the importance of age and, less so, cigarette smoking as factors that influence mutant frequency and suggest that a micronutrient, folic acid, may modify genetic damage at the hprt locus. To the extent that somatic mutation contributes to carcinogenesis, these environmental factors may enhance the risk of developing malignant transformation.
Environ Mol Mutagen 1992
PMID:Factors influencing mutation at the hprt locus in T-lymphocytes: studies in normal women and women with benign and malignant breast masses. 160 Sep 53

The cDNAs for variant estrogen receptor (ER) mRNAs previously identified in human breast cancer biopsy samples have been cloned and characterized. Some of these cDNAs are unique to a tumor sample (e.g. clones 24 and 5), while others are present in multiple breast tumor samples (e.g. clone 4). The 5' ends of the variant cDNAs are essentially identical to sequences present in exons 1, 2, and 3 of the normal ER mRNA. However, at points which mark either the exon 2/intron or exon 3/intron boundaries, the variant cDNA sequences diverge and are unrelated to the normal ER mRNA. The unique sequences of clones 24 and 5 are unknown, and the unique sequence of clone 4 is related to the long interspersed repetitive LINE-1 sequences. The variant mRNAs contain open reading frames which could encode proteins containing known functional domains of the normal ER but missing others. In particular, the hormone binding domain of the normal ER is always missing. Furthermore, some of the variant transcripts may encode other unique proteins. In transient expression assays the proteins encoded by the variant ER mRNAs are unable to activate transcription of an estrogen-responsive reporter gene; neither are they able to modulate the ability of normal ER proteins to activate transcription.
Mol Endocrinol 1992 May
PMID:Characterization of estrogen receptor variant mRNAs from human breast cancers. 160 86

The effect was studied of four different synthetic progestins (Org 30659, gestodene, 3-ketodesogestrel and levonorgestrel) on the proliferation of the 17 beta estradiol (E2)-dependent human breast cancer cell line MCF7. All progestins were found to stimulate proliferation, but only at high pharmacological dosages. Moreover, like estrogens the progestins at high concentrations synergistically stimulated MCF7 cell proliferation together with low concentrations of insulin. This stimulatory effect could be blocked by antiestrogens, but not by antiglucocorticoids and antiprogestins. This suggests that growth stimulation by these progestins (or their metabolites) occurs through crossreaction with the E2 receptor (ER). This is confirmed by the observation that the strong synthetic progestin Org 2058 does not stimulate proliferation. The absence of a progesterone receptor (PR)-mediated growth response seems not to be due to aberrant PR expression in these cells; 27,000 receptors (Kd 1.7 x 10(-10)M) per cell were present under growth-assay conditions. Growth stimulation by E2 in the absence or presence of insulin, is slightly inhibited or unaffected by the progestins, respectively. Our data do not support a role for the recently identified gestodene binding sites [Colletta et al., J. Steroid Biochem. 33 (1989) 1055-1061] in mediating gestodene effects on breast cancer cells: gestodene and 3-ketodesogestrel, a compound that does not bind to these gestodene binding sites, showed a similar biological activity. The effects of the progestins on the MCF7 breast cancer cell line, indicate that the use of these compounds at very high concentrations may be unfavourable, but do not support a role for them in directly stimulating breast tumor proliferation at the low progestin concentration which are reached in the serum in oral contraceptive users.
J Steroid Biochem Mol Biol 1992 Jun
PMID:Effects of progestins on the proliferation of estrogen-dependent human breast cancer cells under growth factor-defined conditions. 161 75

The purpose of our study was to evaluate the effects of 5 alpha-dihydrotestosterone (DHT) and hydroxyflutamide (HF), alone or in combination, on androgen receptor (AR) dynamics and on cellular growth in cultured breast cancer cells (EVSA-T). The incubation of cells with DHT increased the concentration of nuclear AR after 24 and 48 h. HF was also able to promote the nuclear accumulation of AR after 24 and 48 h of treatment. When HF-treated cells are incubated with DHT, the nuclear AR concentration is lower than that found in cells treated with DHT alone. We conclude that HF acts by increasing nuclear accumulation of receptor-antiandrogen complexes. Moreover, DHT stimulates cell growth while HF has an inhibitory effect. Thymidine incorporation in cells also increased after DHT treatment and decreased after HF incubation. The HF-induced inhibition of cell growth persisted both after renewal of the medium and after the addition of DHT to cultures. It may be hypothesized that either DHT is converted to inactive metabolites or that HF exerts a persistent inhibitory effect. In the latter case, the antiandrogen action of HF could be exerted by retention of high levels of antiandrogen in cells or by such a depressed protein synthesis that the renewal of growth is slower than the 48 h period studied.
J Steroid Biochem Mol Biol 1992 Jun
PMID:Effects of dihydrotestosterone and hydroxyflutamide on androgen receptors in cultured human breast cancer cells (EVSA-T). 161 84

The National Biotherapy Study Group (NBSG) conducted a broad phase II trial using interleukin-2 (IL-2) by continuous infusion and alpha interferon (IFN) subcutaneously in 267 patients with a variety of advanced cancers, including 29 with breast cancer, 89 with renal cancer, and 69 with melanoma. IL-2 [18 million international units (MIU)/m2] was given by continuous infusion for 108 hours with 3 mu/m2 subcutaneous IFN every other day during the IL-2 infusion. The patients were treated for 1 week followed by a 2-week rest. After two cycles of treatment, patients were evaluated for response. Of the 237 patients evaluable for response, 20 (8%) had a complete or partial response and 128 (54%) were stable. Therefore, 62% of the evaluable patients were nonprogressive during the first 90 days of IL-2/IFN therapy. The objective response rate was 11% in melanoma, 7% in renal cancer, 14% in breast cancer, and 3% in patients with a variety of malignancies for an overall response rate of 7% in these patients with advanced cancer. The patients were treated on a general medical ward and tolerated treatment well with fatigue and fever being nearly universal. Dyspnea, pruritus, chills, and elevated creatinines were frequent but less common. This combination biotherapy regimen has minimal activity in a variety of advanced cancers and must be compared with the best existing chemotherapy for each cancer type in randomized, prospective trials.
Mol Biother 1992 Mar
PMID:Combination biotherapy utilizing interleukin-2 and alpha interferon in patients with advanced cancer: a National Biotherapy Study Group Trial. 162 72

Estradiol 17 beta-hydroxysteroid dehydrogenase acts to convert estrone to the biologically active estrogen, estradiol, in breast tumors and MCF-7 breast cancer cells in vitro. In this study we have examined the ability of albumin to influence the effect of growth factors (insulin-like growth factor-I (IGF-I), epidermal growth factor (EGF), transforming growth factor-alpha (TGF alpha)) and cytokines (interleukin (IL)-1, IL-6) on estradiol 17 beta-hydroxysteroid dehydrogenase activity in MCF-7 cells. IGF-I (80 ng/ml) or albumin (30 micrograms/ml) stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity by 144% and 102% (p less than 0.01). The combination of IGF-I and albumin, however, produced a marked (704%) synergistic stimulation of estradiol 17 beta-hydroxysteroid dehydrogenase activity. EGF or TGF alpha failed to stimulate estradiol 17 beta-hydroxysteroid dehydrogenase activity and no synergism with albumin was detected. IL-1 (10 ng/ml), but not IL-6, also stimulated estradiol 17 beta-hydroxysteroid dehydrogenase activity and acted synergistically with albumin to stimulate enzyme activity. MCF-7 cells were shown to specifically bind 125I-albumin and binding is increased by pretreatment of cells with IGF-I (80 ng/ml) for 48 h. It is concluded that the synergism that results from treating MCF-7 cells with albumin and IGF-I may result from increased albumin uptake and subsequent biological effect.
Mol Cell Endocrinol 1992 Jun
PMID:Synergistic interaction of growth factors and albumin in regulating estradiol synthesis in breast cancer cells. 163 15


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