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Title:
The influence of tamoxifen on normal mouse mammary gland homeostasis | Breast Cancer Research
Description:
Lineage tracing using inducible genetic labeling has emerged to be a powerful method for interrogating the developmental fate of cells in intact tissues. A common induction mechanism is the use of tamoxifen-dependent Cre recombinase (CreER and CreERT2), but the effects of tamoxifen at doses normally used in lineage-tracing studies on normal adult mammary gland homeostasis are not known. We used flow cytometry and immunostaining of intact glands to determine whether varying doses of tamoxifen skew the distribution and the apoptosis and proliferation status of different types of mammary epithelial cells in vivo. We also examined how tamoxifen influences the number of progenitor and mammary repopulating units (MRUs). Our results indicate that ≥5 mg/25 g body weight of tamoxifen induces a transient increase in cell proliferation and in the number of basal cells in the adult mammary epithelium up to 7 days after tamoxifen administration. However, in the medium term (3 weeks), all doses of tamoxifen ≥1 mg/25 g body weight result in a decrease in the number of basal and EpCAM+CD49b− luminal cells and a decrease in progenitor cell function. Tamoxifen at doses ≥5 mg/25 g body weight induced a transient increase in caspase-3-mediated apoptotic cell death within the mammary epithelium. However, mammary epithelial cell numbers in all subpopulations were restored to their original levels by 8 weeks. No long-lasting effects of tamoxifen on MRU numbers or on pubertal ductal development were observed. Tamoxifen can skew the distribution of mammary cell types in a dose-dependent manner, and thus caution must be taken when interpreting lineage-tracing studies using high doses of tamoxifen, particularly when short-duration analyses of a quantitative nature are being performed.
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Keywords {🔍}
tamoxifen, mammary, cells, cell, mice, doses, pubmed, article, figure, glands, google, scholar, days, cas, cancer, gland, number, epithelium, basal, luminal, epithelial, observed, effects, file, mouse, apoptosis, oil, dose, additional, data, increase, breast, proliferation, stem, time, authors, analysis, lineagetracing, experiments, inguinal, lineage, results, day, tracing, transient, high, populations, injection, analyzed, tamoxifentreated,
Topics {✒️}
doxycycline-inducible k14-rtta/teto-cre mice wnt/beta-catenin-responsive stem cells renée van amerongen ligand-activated site-specific recombination + 5 μg/ml insulin + 10 μm y-27632 tamoxifen-induced creert2-mediated recombination article download pdf terminal-end bud structures kluwer academic/plenum press interpreting lineage-tracing studies normal pre-menopausal women inducible lineage-tracing studies breast cancer research mammary lineage-tracing studies collectively termed lin + cells induce short-term proliferation long-term adjuvant therapy van amerongen single short-term exposure cancer research uk flow-cytometry gating strategy anti-rat antibody conjugated author information authors tamoxifen-dependent cre recombinase transient short-term increase tamoxifen-inducible cre-er cambridge research institute related subjects injected wild-type c57bl/6 mouse mammary gland advanced breast cancer breast cancer patient nat rev cancer developmental stage-specific contribution breast cancer res inducible lineage tracing progenitor cell function breast cancer cells privacy choices/manage cookies mouse mammary epithelial netherlands cancer institute mammary gland development estrogen receptor beta epcam+cd49b− luminal cells jordan vc lineage-tracing studies cell-division kinetics cre recombinase activity mouse mammary epithelium similar dose-dependent effect
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headline:The influence of tamoxifen on normal mouse mammary gland homeostasis
description:Lineage tracing using inducible genetic labeling has emerged to be a powerful method for interrogating the developmental fate of cells in intact tissues. A common induction mechanism is the use of tamoxifen-dependent Cre recombinase (CreER and CreERT2), but the effects of tamoxifen at doses normally used in lineage-tracing studies on normal adult mammary gland homeostasis are not known. We used flow cytometry and immunostaining of intact glands to determine whether varying doses of tamoxifen skew the distribution and the apoptosis and proliferation status of different types of mammary epithelial cells in vivo. We also examined how tamoxifen influences the number of progenitor and mammary repopulating units (MRUs). Our results indicate that ≥5 mg/25 g body weight of tamoxifen induces a transient increase in cell proliferation and in the number of basal cells in the adult mammary epithelium up to 7 days after tamoxifen administration. However, in the medium term (3 weeks), all doses of tamoxifen ≥1 mg/25 g body weight result in a decrease in the number of basal and EpCAM+CD49b− luminal cells and a decrease in progenitor cell function. Tamoxifen at doses ≥5 mg/25 g body weight induced a transient increase in caspase-3-mediated apoptotic cell death within the mammary epithelium. However, mammary epithelial cell numbers in all subpopulations were restored to their original levels by 8 weeks. No long-lasting effects of tamoxifen on MRU numbers or on pubertal ductal development were observed. Tamoxifen can skew the distribution of mammary cell types in a dose-dependent manner, and thus caution must be taken when interpreting lineage-tracing studies using high doses of tamoxifen, particularly when short-duration analyses of a quantitative nature are being performed.
datePublished:2014-07-24T00:00:00Z
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Tamoxifen
Mammary Gland
Mammary Epithelium
Luminal Progenitor
Tamoxifen Dose
Cancer Research
Oncology
Surgical Oncology
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headline:The influence of tamoxifen on normal mouse mammary gland homeostasis
description:Lineage tracing using inducible genetic labeling has emerged to be a powerful method for interrogating the developmental fate of cells in intact tissues. A common induction mechanism is the use of tamoxifen-dependent Cre recombinase (CreER and CreERT2), but the effects of tamoxifen at doses normally used in lineage-tracing studies on normal adult mammary gland homeostasis are not known. We used flow cytometry and immunostaining of intact glands to determine whether varying doses of tamoxifen skew the distribution and the apoptosis and proliferation status of different types of mammary epithelial cells in vivo. We also examined how tamoxifen influences the number of progenitor and mammary repopulating units (MRUs). Our results indicate that ≥5 mg/25 g body weight of tamoxifen induces a transient increase in cell proliferation and in the number of basal cells in the adult mammary epithelium up to 7 days after tamoxifen administration. However, in the medium term (3 weeks), all doses of tamoxifen ≥1 mg/25 g body weight result in a decrease in the number of basal and EpCAM+CD49b− luminal cells and a decrease in progenitor cell function. Tamoxifen at doses ≥5 mg/25 g body weight induced a transient increase in caspase-3-mediated apoptotic cell death within the mammary epithelium. However, mammary epithelial cell numbers in all subpopulations were restored to their original levels by 8 weeks. No long-lasting effects of tamoxifen on MRU numbers or on pubertal ductal development were observed. Tamoxifen can skew the distribution of mammary cell types in a dose-dependent manner, and thus caution must be taken when interpreting lineage-tracing studies using high doses of tamoxifen, particularly when short-duration analyses of a quantitative nature are being performed.
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Mammary Gland
Mammary Epithelium
Luminal Progenitor
Tamoxifen Dose
Cancer Research
Oncology
Surgical Oncology
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