title: Hes1 is required for contact inhibition of cell proliferation in 3T3-L1 preadipocytes.
abstract: Cell-cell contact causes the growth arrest of cells in culture, which is referred to as contact inhibition of cell proliferation. Notch signaling is involved in the growth arrest of cells represented by contact inhibition of cell proliferation. The Notch effector, Hes1 (Hairy and enhancer of split 1), promotes or inhibits cell proliferation by repressing the expression of cyclin-dependent kinase inhibitors. However, it is still unclear whether Hes1 is involved in the mechanisms responsible for contact inhibition of cell proliferation. Here, we examined the involvement of Hes1 in contact inhibition of cell proliferation using a γ-secretase inhibitor and a stable 3T3-L1 preadipocyte cell line expressing Hes1-shRNA as a model cell. The cell cycle was not arrested in Hes1-knockdown cells even after the cells reached confluence. Reduced Hes1 levels failed to repress the expression of E2F-1, a transcription factor required for the progression of the cell cycle. The expression of Myc, cyclin E1, and cyclin A2 in E2F-1 target genes was also higher in Hes1-knockdown cells compared with the negative control. These results suggest that Hes1 plays essential roles in contact inhibition of cell proliferation in 3T3-L1 cells by repressing E2F-1 expression.
authors.affiliation: Department of Physiology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Noda
authors.forename: Sato
authors.initials: S
authors.lastname: Honma
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ohmiya
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003260:Contact Inhibition / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D051880:Receptors, Notch / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004151:Dipeptides; D004791:Enzyme Inhibitors; D018398:Homeodomain Proteins; D051880:Receptors, Notch; D000072056:Transcription Factor HES-1; C493957:Cdkn1a protein, mouse; C493961:Cdkn1b protein, mouse; C489734:Hes1 protein, mouse; C419410:N-(N-(3,5-difluorophenacetyl)alanyl)phenylglycine tert-butyl ester