title: The role of unfolded protein response in differentiation of mammary epithelial cells.
abstract: The accumulation of misfolded proteins in the ER provokes ER stress by increasing the demand for energy, chaperones, and other proteins that are needed to fold client proteins or to degrade unfoldable secretory cargo. This stress activates a signaling network called the unfolded protein response (UPR). However, recent accumulated data suggested that the UPR also provides important signals for regulating cell differentiation and maturation. However, the relationship between UPR and mammary gland development has not been fully elucidated. To define the involvement of the UPR in mammary gland development, mammary glands were collected from non-pregnant mice, at days 5, 10 and 15 of pregnancy, at days 1 and 7 of lactation, and the expression patterns of UPR-related genes were determined by real-time PCR. We found that the mRNA expression of ATF4 and XBP1 significant increased during pregnancy. Moreover, we found that both ATF4 and XBP1 proteins are expressed in mammary epithelial cells by immunohistological analysis. In order to know the role of ATF4 and XBP1 in the differentiation of mammary epithelial cell, we performed gene knockdown experiment using HC11 cells. We found that ATF4 or XBP1 knockdown suppressed the mRNA expression of beta-casein and lactogenic hormone receptor in differentiating HC11 cells. Our results demonstrate that XBP1 and ATF4, which are UPR-related transcription factors, directly or indirectly participate in cell differentiation mechanisms through the regulation of the expression of lactogenic hormone receptors in mouse mammary epithelial cells.
authors.affiliation: Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Tsuchiya
authors.affiliation: Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Koizumi
authors.affiliation: Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Hayashi
authors.affiliation: Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Hanaoka
authors.affiliation: Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan.
authors.forename: Yukako
authors.initials: Y
authors.lastname: Tokutake
authors.affiliation: Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan; Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan; Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan. Electronic address: yonekura@shinshu-u.ac.jp.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yonekura
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D059865:Endoplasmic Reticulum Stress / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology* / Q000502:physiology*; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D056811:Unfolded Protein Response / Q000502:physiology*
keywords: Differentiation; Mammary epithelial cell; UPR