title: Meis1 regulates epidermal stem cells and is required for skin tumorigenesis.
abstract: Previous studies have shown that Meis1 plays an important role in blood development and vascular homeostasis, and can induce blood cancers, such as leukemia. However, its role in epithelia remains largely unknown. Here, we uncover two roles for Meis1 in the epidermis: as a critical regulator of epidermal homeostasis in normal tissues and as a proto-oncogenic factor in neoplastic tissues. In normal epidermis, we show that Meis1 is predominantly expressed in the bulge region of the hair follicles where multipotent adult stem cells reside, and that the number of these stem cells is reduced when Meis1 is deleted in the epidermal tissue of mice. Mice with epidermal deletion of Meis1 developed significantly fewer DMBA/TPA-induced benign and malignant tumors compared with wild-type mice, suggesting that Meis1 plays a role in both tumor development and malignant progression. This is consistent with the observation that Meis1 expression increases as tumors progress from benign papillomas to malignant carcinomas. Interestingly, we found that Meis1 localization was altered to neoplasia development. Instead of being localized to the stem cell region, Meis1 is localized to more differentiated cells in tumor tissues. These findings suggest that, during the transformation from normal to neoplastic tissues, a functional switch occurs in Meis1.
authors.affiliation: Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Saito
authors.affiliation: Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Isogai
authors.affiliation: Department of Biosciences and Informatics, Bioinfomatics Laboratory, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Aoto
authors.affiliation: Department of Biosciences and Informatics, Bioinfomatics Laboratory, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hachiya
authors.affiliation: Department of Biosciences and Informatics, Bioinfomatics Laboratory, Keio University, Yokohama, Kanagawa, Japan.
authors.forename: Yasubumi
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Katsuragi
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hirose
authors.affiliation: Department of Molecular Genetics, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Niigata, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Kominami
authors.affiliation: Division of Development and Aging, Research Institute for Biological Science, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Goitsuka
authors.affiliation: Division of Carcinogenesis, Cancer Institute, Japanese Foundation for Cancer Research, Koto, Tokyo, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Carcinogenesis Research, Division of Experimental Animal Research, Chiba Cancer Center Research Institute, Chiba, Chiba, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Wakabayashi
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene; D053687:Adult Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002273:Carcinogens; D002277:Carcinoma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D018859:Hair Follicle / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018398:Homeodomain Proteins / Q000235:genetics*; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D039902:Multipotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000172:deficiency / Q000235:genetics*; D010212:Papilloma / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives
chemical_list: D002273:Carcinogens; D018398:Homeodomain Proteins; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D015127:9,10-Dimethyl-1,2-benzanthracene; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D013755:Tetradecanoylphorbol Acetate