Requirement for IGF-I in epidermal growth factor-mediated cell cycle progression of mammary epithelial cells.
Induction of cyclin proteins is required for progression of cells through the G(1)-S and G(2)-M cell cycle checkpoints and is a primary mechanism by which mitogens regulate cell cycle progression. IGF-I and the epidermal growth factor (EGF)-related ligands are mitogens for mammary epithelial cells in vitro and are essential for growth of the mammary epithelium during development. We report here that IGF-I in combination with EGF or TGFalpha is synergistic in promoting DNA synthesis in mammary epithelial cells in the intact mammary gland cultured in vitro. We further investigated the role of IGF-I and EGF in cyclin expression and cell cycle progression in the mammary gland and demonstrate that IGF-I and EGF induce expression of early G(1) cyclins. However, we show that IGF-I, but not EGF, induces late G(1) and G(2) cyclins and is required for mammary epithelial cells to overcome the G(1)-S checkpoint. These data demonstrate that IGF-I is essential for cell cycle progression in mammary epithelial cells and that it is required for EGF-mediated progression past the G(1)-S checkpoint in these cells.
Stull
Malinda A
MA
Department of Neuroscience & Anatomy H109, Penn State College of Medicine, 500 University Drive, Hershey, Pennsylvania 17033.
Richert
Monica M
MM
Loladze
Aimee V
AV
Wood
Teresa L
TL
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D056746:Cyclin G; D056766:Cyclin G1; D056767:Cyclin G2; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004261:DNA Replication / Q000502:physiology; D004815:Epidermal Growth Factor / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D008024:Ligands; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D023282:Nuclease Protection Assays; D009924:Organ Culture Techniques
C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D056767:Cyclin G2; D016213:Cyclins; D008024:Ligands; D004815:Epidermal Growth Factor; D007334:Insulin-Like Growth Factor I; D004247:DNA