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- Palmieri, C, et al.
(författare)
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Estrogen receptor beta in breast cancer
- 2002
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Ingår i: Endocrine-related cancer. - : Bioscientifica. - 1351-0088. ; 9:1, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen is essential for normal growth and differentiation in the mammary gland. It also supports growth of approximately 50% of primary breast cancers. For this reason, removal of estrogen or blocking of its action with the anti-estrogen, tamoxifen, is the main treatment for estrogen receptor alpha (ERalpha)-positive tumors. In 1996, when oncologists became aware of a second ER, ERbeta, there was some doubt as to whether this receptor would be of importance in breast cancer because the clinical consensus was that responsiveness to tamoxifen is related to the presence of ERalpha in breast cancer. Today we know that ERalpha and ERbeta have distinct cellular distributions, regulate separate sets of genes and can oppose each other's actions on some genes. We also know that ERbeta is widely expressed in both the normal and malignant breast and that there are proliferating cells in the breast which express ERbeta. In this review we summarize what is known about ERbeta in breast cancer and examine the possibility that ERbeta-selective ligands may well represent a useful class of pharmacological tools with a novel target, namely proliferating cells expressing ERbeta.
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| 7. |
- Saji, S, et al.
(författare)
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Estrogen receptors alpha and beta in the rodent mammary gland
- 2000
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 97:1, s. 337-342
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Tidskriftsartikel (refereegranskat)abstract
- An obligatory role for estrogen in growth, development, and functions of the mammary gland is well established, but the roles of the two estrogen receptors remain unclear. With the use of specific antibodies, it was found that both estrogen receptors, ERα and ERβ, are expressed in the rat mammary gland but the presence and cellular distribution of the two receptors are distinct. In prepubertal rats, ERα was detected in 40% of the epithelial cell nuclei. This decreased to 30% at puberty and continued to decrease throughout pregnancy to a low of 5% at day 14. During lactation there was a large induction of ERα with up to 70% of the nuclei positive at day 21. Approximately 60–70% of epithelial cells expressed ERβ at all stages of breast development. Cells coexpressing ERα and ERβ were rare during pregnancy, a proliferative phase, but they represented up to 60% of the epithelial cells during lactation, a postproliferative phase. Western blot analysis and sucrose gradient centrifugation confirmed this pattern of expression. During pregnancy, the proliferating cell nuclear antigen was not expressed in ERα-positive cells but was observed in 3–7% of ERβ-containing cells. Because more than 90% of ERβ-bearing cells do not proliferate, and 55–70% of the dividing cells have neither ERα nor ERβ, it is clear that the presence of these receptors in epithelial cells is not a prerequisite for estrogen-mediated proliferation.
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- Palmieri, C, et al.
(författare)
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The expression of oestrogen receptor (ER)-beta and its variants, but not ERalpha, in adult human mammary fibroblasts
- 2004
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Ingår i: Journal of molecular endocrinology. - : Bioscientifica. - 0952-5041 .- 1479-6813. ; 33:1, s. 35-50
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Tidskriftsartikel (refereegranskat)abstract
- Whilst oestrogen receptor (ER)-alpha and ERbeta have been shown to be important in the development of the mammary gland, the cell-specific expression pattern of these two receptors within the human breast is not clear. Although it is well established that in the developing rodent mammary gland stromal ERalpha mediates the secretion of growth factors which stimulate the proliferation of the ductal epithelium, the expression of ERalpha in human adult breast stromal fibroblasts is controversial, and the expression of ERbeta has not been properly defined. In the present study, we have evaluated the expression of ERalpha and ERbeta by immunohistochemistry in normal tissue samples, and in purified human breast fibroblasts by Western blotting, RT-PCR analysis and ligand-binding sucrose gradient assay. Our data clearly demonstrated that ERbeta variants, including ERbeta1, ERbeta2, ERbeta5, ERbetadelta and ERbetains, but not ERalpha, are expressed in human adult mammary fibroblasts. These results are supported by the findings that an ERbeta-selective ligand, BAG, but not the ERalpha high-affinity ligand oestradiol, can induce fibroblast growth factor-7 release and activate transcription from an oestrogen-responsive element promoter in these adult human mammary fibroblasts. Together, these observations revealed that, in the adult breast and in breast cancer, the proliferative signals derived from the stroma of adult mammary glands in response to oestrogen are not mediated by ERalpha and provide new insights into the nature of stromal-epithelial interactions in the adult mammary gland. In addition, the expression of these ERbeta variants in cells where there is no ERalpha suggested that these ERbeta splice forms may have functions other than that of modulating ERalpha activity.
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- Saji, N. S., et al.
(författare)
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Hadean geodynamics inferred from time-varying 142Nd/144Nd in the early Earth rock record
- 2018
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Ingår i: Geochemical Perspectives Letters. ; 7, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- Tracking the secular evolution of 142Nd/144Nd anomalies is important towards understanding the crust-mantle dynamics in the early Earth. Excessive scatter in the published data, however, precludes identifying the fine structure of 142Nd/144Nd evolution as the expected variability is on the order of few parts per million. We report ultra-high precision 142Nd/144Nd data for Eoarchean and Palaeoarchean rocks from the Isua Supracrustal Belt (SW Greenland) that show a well-resolved 142Nd/144Nd temporal variability suggesting progressive convective homogenisation of the Hadean Isua depleted mantle. This temporally decreasing 142Nd/144Nd signal provides a direct measure of early mantle dynamics, defining a stirring timescale of <250 Myr consistent with vigorous convective stirring in the early mantle. The 142Nd/144Nd evolution suggests protracted crustal residence times of ~1000-2000 Myr, inconsistent with modern-style plate tectonics in the Archean. In contrast, a stagnant-lid regime punctuated by episodes of mantle overturns accounts for the long life-time estimated here for the Hadean proto-crust.
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| 13. |
- Saji, S, et al.
(författare)
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Quantitative analysis of estrogen receptor proteins in rat mammary gland
- 2001
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170. ; 142:7, s. 3177-3186
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor α and β proteins (ERα and ERβ) at various stages of development of the rat mammary gland were quantified by Western blotting. ERα and ERβ recombinant proteins were used as standards, and their molar concentrations were measured by ligand binding assays. In 3-week-old pregnant, lactating, and postlactating rats the ERα content ranged from 0.30–1.55 fmol/μg total protein (mean values). The ERβ content of the same samples ranged between 1.06–7.50 fmol/μg total protein. At every developmental stage, the ERβ content of the mammary gland was higher than that of ERα. When receptor levels were normalized against β-actin, it was evident that ER expression changed during development, with maximum expression of both receptors during the lactation period. With an antibody raised against the 18-amino acid insert of the ERβ variant, originally called ERβ2 but named ERβins in this paper, Western blots revealed that ERβins protein was up-regulated during the lactation period. RT-PCR showed that the levels of messenger RNA of ERβins paralleled those of the protein. Double immunohistochemical staining with anti-ERα and anti-ERβins antibodies revealed that ERβins protein colocalized with ERα in 70–80% of the ERα-expressing epithelial cells during lactation and with 30% of these cells during pregnancy. These observations indicate that expression of ERβins is regulated not only quantitatively, but also with regard to its cellular distribution. As ERβins acts as the dominant repressor of ERα, we suggest that its coexpression with ERα quenches ERα function and may be one of the factors that contribute to the previously described insensitivity of the mammary gland to estrogens during lactation.
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| 14. |
- Suzuki, R, et al.
(författare)
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Alcohol and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status : A prospective cohort study
- 2005
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Ingår i: Journal of the National Cancer Institute. - Karolinska Inst, Div Nutr Epidemiol, Natl Inst Environm Med, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden. Tokyo Metropolitan Komagome Hosp, Dept Surg & Breast Oncol, Tokyo Metropolitan Canc & Infect Dis Ctr, Tokyo, Japan. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. : OXFORD UNIV PRESS INC. - 0027-8874 .- 1460-2105. ; 97:21, s. 1601-1608
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alcohol intake has been reported to be positively associated with an increased risk of postmenopausal breast cancer; however, the association with the estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors remains unclear. Methods: Self-reported data on alcohol consumption were collected in 1987 and 1997 from 51847 postmenopausal women in the population-based Swedish Mammography Cohort. Through June 30,2004,1188 invasive breast cancer case patients with known ER and PR status were identified during an average 8.3-year follow-up. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of breast cancer, adjusting for age; family history of breast cancer; body mass index; height; parity; age at menarche, first birth, and menopause; education level; use of postmenopausal hormones; and diet. Heterogeneity among groups was evaluated using the Wald test. All statistical tests were two-sided. Results: Alcohol consumption was associated with an increased risk for the development of ER-positive (+) tumors, irrespective of PR status (highest intake [ >= 10 g of alcohol per day] versus nondrinkers, multivariable RR = 1.35, 95% confidence interval [CI] = 1.02 to 1.80; P-trend < .049 for ER+PR+ tumors; and RR = 2.36, 95% CI = 1.56 to 3.56; P-trend < .001 for ER+PR-tumors). The absolute rate of ER+ breast cancer (standardized to the age distribution of person-years experienced by all study participants using 5-year age categories) was 232 per 100000 person-years among women in the highest category of alcohol intake, and 158 per 100000 person-years among nondrinkers. No association was observed between alcohol intake and the risk of developing ER-tumors. Furthermore, we observed a statistically significant interaction between alcohol intake and the use of postmenopausal hormones on the risk for ER+PR+ tumors (P-interaction = .039). Conclusion: The observed association between risk of developing postmenopausal ER+ breast cancer and alcohol drinking, especially among those women who use postmenopausal hormones, may be important, because the majority of breast tumors among postmenopausal women overexpress ER.
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| 16. |
- Suzuki, R., et al.
(författare)
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Dietary lignans and postmenopausal breast cancer risk by oestrogen receptor status : a prospective cohort study of Swedish women
- 2008
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 98:3, s. 636-640
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Tidskriftsartikel (refereegranskat)abstract
- Among the 51 823 postmenopausal women in the Swedish Mammography Cohort, we investigated breast cancer risk in relation to the FFQ-based estimated lignan intake by oestrogen receptor (ER) and progesterone receptor (PR) subtypes. A significant 17% risk reduction for breast cancer overall in the high lignan quartile was observed, especially among PMH user (P-interaction < 0.010), but no heterogeneity across ER/PR subtypes.
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