BACKGROUND: Long-lived somatic cells such as stem/progenitor cells may progressively accumulate oncogenic mutations and cause cancer. Some evidence suggests that pre-menopausal administration of progesterone confers a long-term increased risk of breast cancer. AIM: To clarify the effect of progesterone on long-lived mammary epithelial cells in rats. MATERIALS AND METHODS: Female Sprague- Dawley rats (3 and 7 weeks of age) were implanted sc with 14-day slow-release pellets of 5-bromo-2'-deoxyuridine (BrdU) and were sacrificed every 2 weeks between 0 and 10 weeks after the release period. Some rats at 7 weeks of age were also implanted with progesterone and sacrificed 0 or 10 weeks after the release period. Mammary glands were examined by immunohistochemistry and immunofluorescence for BrdU, proliferative cell nuclear antigen (PCNA) and progesterone receptor (PR). RESULTS: After BrdU labeling of 3- and 7-week-old rats, the BrdU index decreased gradually over 10 weeks and resulted in small fractions (1-3%) of label-retaining epithelial cells (LREC) 10 weeks after BrdU labeling in both mammary lobules and ducts. Treatment with progesterone during labeling significantly increased the fraction of long-lived LREC in lobules and ducts by 9- and 4-fold, respectively. The long-lived LREC population in the ducts was enriched for PCNA- and PR-positive cells, but the percentage of positive cells was not affected by progesterone in either lobules or ducts. CONCLUSIONS: Progesterone stimulates proliferation of a long-lived epithelial cell population in the mammary lobules and ducts of rats. Such cells in the duct are characterized by a high proliferation rate and PR expression.
BACKGROUND: Long-lived somatic cells such as stem/progenitor cells may progressively accumulate oncogenic mutations and cause cancer. Some evidence suggests that pre-menopausal administration of progesterone confers a long-term increased risk of breast cancer. AIM: To clarify the effect of progesterone on long-lived mammary epithelial cells in rats. MATERIALS AND METHODS: Female Sprague- Dawley rats (3 and 7 weeks of age) were implanted sc with 14-day slow-release pellets of 5-bromo-2'-deoxyuridine (BrdU) and were sacrificed every 2 weeks between 0 and 10 weeks after the release period. Some rats at 7 weeks of age were also implanted with progesterone and sacrificed 0 or 10 weeks after the release period. Mammary glands were examined by immunohistochemistry and immunofluorescence for BrdU, proliferative cell nuclear antigen (PCNA) and progesterone receptor (PR). RESULTS: After BrdU labeling of 3- and 7-week-old rats, the BrdU index decreased gradually over 10 weeks and resulted in small fractions (1-3%) of label-retaining epithelial cells (LREC) 10 weeks after BrdU labeling in both mammary lobules and ducts. Treatment with progesterone during labeling significantly increased the fraction of long-lived LREC in lobules and ducts by 9- and 4-fold, respectively. The long-lived LREC population in the ducts was enriched for PCNA- and PR-positive cells, but the percentage of positive cells was not affected by progesterone in either lobules or ducts. CONCLUSIONS:Progesterone stimulates proliferation of a long-lived epithelial cell population in the mammary lobules and ducts of rats. Such cells in the duct are characterized by a high proliferation rate and PR expression.
Authors: Bryan E Welm; Stacey B Tepera; Teresa Venezia; Timothy A Graubert; Jeffrey M Rosen; Margaret A Goodell Journal: Dev Biol Date: 2002-05-01 Impact factor: 3.582
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Authors: J Dinny Graham; Patricia A Mote; Usha Salagame; Jessica H van Dijk; Rosemary L Balleine; Lily I Huschtscha; Roger R Reddel; Christine L Clarke Journal: Endocrinology Date: 2009-04-02 Impact factor: 4.736
Authors: Mark A Feitelson; Alla Arzumanyan; Rob J Kulathinal; Stacy W Blain; Randall F Holcombe; Jamal Mahajna; Maria Marino; Maria L Martinez-Chantar; Roman Nawroth; Isidro Sanchez-Garcia; Dipali Sharma; Neeraj K Saxena; Neetu Singh; Panagiotis J Vlachostergios; Shanchun Guo; Kanya Honoki; Hiromasa Fujii; Alexandros G Georgakilas; Alan Bilsland; Amedeo Amedei; Elena Niccolai; Amr Amin; S Salman Ashraf; Chandra S Boosani; Gunjan Guha; Maria Rosa Ciriolo; Katia Aquilano; Sophie Chen; Sulma I Mohammed; Asfar S Azmi; Dipita Bhakta; Dorota Halicka; W Nicol Keith; Somaira Nowsheen Journal: Semin Cancer Biol Date: 2015-04-17 Impact factor: 15.707