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Induction of differentiation of the cultured rat mammary epithelial cells by triterpene acids

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Abstract

We investigated the effects of triterpene acids (TAs), ursolic acid (UA) and oleanolic acid (OA), on the induction of proliferation and differentiation of normal rat mammary epithelial cells (RMEC) or organoids cultured in Matrigel or primary culture system. To elucidate the effects, we tested their differentiation inducing activities with intercellular communication ability, cell cycle patterns, induction of apoptosis, and morphological differentiation in the three dimensional extracellular culture system. To study the changes of RMEC subpopulation in culture, the cultured cells were isolated, immunostained with peanut lectin (PNA) and anti-Thy-1.1 antibody and then analyzed with flow cytometry. Four different subpopulations, such as PNA and Thy-1.1 negative cells (B-), PNA positive cells (PNA+), Thy-1.1 positive cells (Thy-1.1+), PNA and Thy-1.1 positive cells (B+), were obtained and the size of each subpopulation was changed in culture with time in the presence of TAs. Intercellular communication was observed in culture for 7 days in TAs-treated cells, but not in culture for 4 days with scrape-loading dye transfer technique. G2/M phase cells and the number of apoptotic population were increased in TAs-treated groups in cell cycle analyses. S phase fractions were reduced and the change of G1 phase cells was not observed. The colonies with distinct multicellular structures, such as stellate, ductal, webbed, squamous, lobulo-ductal colonies, were observed in Matrigel culture and the frequencies of each colony were changed in the presence of TAs. These results suggest that UA and OA have differentiation inducing effects on rat mammary epithelial cells in primary or in Matrigel culture.

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Authors and Affiliations

  1. Department of Pharmacy, Pusan National University, 609-735, Pusan, Korea

    Kee-Joo Paik, Seong-Sill Jeon, Hae-Young Chung, Kyung Hee Lee & Nam Deuk Kim

  2. Department of Molecular Biology, Pusan National University, 609-735, Pusan, Korea

    Kyu-Won Kim

  3. Pusan Cancer Research Center, Pusan National University, 609-735, Pusan, Korea

    Kyu-Won Kim

  4. Department of Aquatic Life Medicine, College of Fisheries Sciences, Pukyong National University, 608-737, Pusan, Korea

    Joon-Ki Chung

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  1. Kee-Joo Paik
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Paik, KJ., Jeon, SS., Chung, HY. et al. Induction of differentiation of the cultured rat mammary epithelial cells by triterpene acids. Arch. Pharm. Res. 21, 398–405 (1998). https://doi.org/10.1007/BF02974633

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  • DOI: https://doi.org/10.1007/BF02974633

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