title: B-Myb enhances proliferation and suppresses differentiation of keratinocytes in three-dimensional cell culture.
abstract: B-Myb (Mybl2) is a member of the Myb gene family of transcription factors involved in the control of cell growth, differentiation, and apoptosis. The effects of B-Myb on keratinocyte proliferation and differentiation have not yet been clarified. The present study was performed to examine the role of B-Myb in proliferation and differentiation of the spontaneously immortalized human skin keratinocyte cell line HaCaT and normal human keratinocytes with formation of a stratified epidermoid structure in air-liquid interface three-dimensional culture. B-Myb was expressed specifically in undifferentiated normal keratinocytes and downregulated during differentiation. The constitutive overexpression of B-Myb in HaCaT cells during air exposure-induced differentiation resulted in an undifferentiated phenotype, i.e., thickening of the stratified layers, suppression of differentiation marker expression, and retention of proliferative activity with activation of cell cycle regulatory proteins in the S and G2/M phases. In contrast, suppression of B-Myb caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that B-Myb plays an important role in maintenance of the undifferentiated phenotype of keratinocytes in the basal epidermal layer.
authors: Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, 305-8575, Japan.
authors: Hiroshi
authors: H
authors: Maruyama
authors: Yosuke
authors: Y
authors: Ishitsuka
authors: Yasuhiro
authors: Y
authors: Fujisawa
authors: Junichi
authors: J
authors: Furuta
authors: Mitsuru
authors: M
authors: Sekido
authors: Yasuhiro
authors: Y
authors: Kawachi
mesh_terms: D018929:Cell Culture Techniques; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics*; D004848:Epithelium / Q000473:pathology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D012867:Skin / Q000166:cytology / Q000473:pathology; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; C064352:MYBL2 protein, human; D034741:RNA, Small Interfering; D015534:Trans-Activators