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Progesterone stimulates progenitor cells in normal human breast and breast cancer cells | Breast Cancer Research and Treatment
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The epithelium of the human breast is made up of a branching ductalālobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormones, progesterone (P) and 17β-estradiol, are critical in driving this normal breast development, yet ovarian activity has also been shown to be a major driver of breast cancer risk. We previously demonstrated that P treatment increases proliferation and augments the number of progenitor-like cells, and that the progesterone receptor (PR) is also expressed in the bipotent progenitor-enriched subfraction. Here we demonstrate that PR is expressed in a subset of CD10+ basal cells and that P stimulates this CD10+ cell compartment, which is enriched for bipotent progenitor activity. In addition, we have shown that P stimulates progenitor cells in human breast cancer cell lines and expands the cancer stem cell population via increasing the stem-like CD44+ population. As changes in cell type composition are one of the hallmark features of breast cancer progression, the demonstration that progenitor cells are stimulated by P in both normal breast and in breast cancer cells has critical implications in discerning the mechanisms of how P increases breast cancer risk.
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pubmed, cancer, article, breast, google, scholar, cas, cells, cell, human, stem, mammary, progesterone, clarke, normal, hormone, central, res, research, progenitor, luminal, natl, basal, access, nature, treatment, hilton, huschtscha, graham, development, receptor, progenitors, epithelial, mote, westmead, institute, privacy, cookies, content, study, steroid, estrogen, receptors, anderson, cycle, gland, stingl, sci, usa, represents,
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month download article/chapter asselin-labat ml aberrant luminal progenitors branching ductalālobular system ep-cam/cd49f markers myoepithelial cells paracrine fgf/tbx3 signaling adult human breast widespread estrogen-dependent repression predominant stem/progenitor marker progestin-driven mammary cancer epithelial progenitors hormone replacement therapy full article pdf multipotent progenitors mammary epithelial cells stem/progenitor cells bipotent progenitor-enriched subfraction mouse mammary gland changed lineage composition cancer stem cells human mammary epithelia luminal cells surrounded starting hormone therapy neglected hormone coming hormone-responsive model estrogen receptors segregate stimulates progenitor cells check access instant access ferguson dj human breast carcinoma cancer stem cell breast cancer cells privacy choices/manage cookies human breast cancer stem cell hierarchy steroid hormone signalling human breast development experimental mammary cancer growth factor pathways keller pj oncogene 32 ļæ½restingā human breast breast tumor heterogeneity medical research council normal human breast medical research institute breast cancer risk relative mrna levels
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headline:Progesterone stimulates progenitor cells in normal human breast and breast cancer cells
description:The epithelium of the human breast is made up of a branching ductalālobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormones, progesterone (P) and 17β-estradiol, are critical in driving this normal breast development, yet ovarian activity has also been shown to be a major driver of breast cancer risk. We previously demonstrated that P treatment increases proliferation and augments the number of progenitor-like cells, and that the progesterone receptor (PR) is also expressed in the bipotent progenitor-enriched subfraction. Here we demonstrate that PR is expressed in a subset of CD10+ basal cells and that P stimulates this CD10+ cell compartment, which is enriched for bipotent progenitor activity. In addition, we have shown that P stimulates progenitor cells in human breast cancer cell lines and expands the cancer stem cell population via increasing the stem-like CD44+ population. As changes in cell type composition are one of the hallmark features of breast cancer progression, the demonstration that progenitor cells are stimulated by P in both normal breast and in breast cancer cells has critical implications in discerning the mechanisms of how P increases breast cancer risk.
datePublished:2014-01-07T00:00:00Z
dateModified:2014-01-07T00:00:00Z
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Progesterone
Progenitor
Breast cancer
Cell lineage
Oncology
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description:The epithelium of the human breast is made up of a branching ductalālobular system, which is lined by a single layer of luminal cells surrounded by a contractile basal cell layer. The co-ordinated development of stem/progenitor cells into these luminal and basal cells is fundamentally important for breast morphogenesis. The ovarian steroid hormones, progesterone (P) and 17β-estradiol, are critical in driving this normal breast development, yet ovarian activity has also been shown to be a major driver of breast cancer risk. We previously demonstrated that P treatment increases proliferation and augments the number of progenitor-like cells, and that the progesterone receptor (PR) is also expressed in the bipotent progenitor-enriched subfraction. Here we demonstrate that PR is expressed in a subset of CD10+ basal cells and that P stimulates this CD10+ cell compartment, which is enriched for bipotent progenitor activity. In addition, we have shown that P stimulates progenitor cells in human breast cancer cell lines and expands the cancer stem cell population via increasing the stem-like CD44+ population. As changes in cell type composition are one of the hallmark features of breast cancer progression, the demonstration that progenitor cells are stimulated by P in both normal breast and in breast cancer cells has critical implications in discerning the mechanisms of how P increases breast cancer risk.
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Progenitor
Breast cancer
Cell lineage
Oncology
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