Regulation of proliferation-specific and differentiation-specific genes during senescence of human epidermal keratinocyte and mammary epithelial cells.
The expression of proliferation-associated genes, cdc2 and E2F-1 and squamous-specific genes transglutaminase type I and cornifin were examined in senescing human epidermal keratinocytes. Cultured keratinocytes underwent 34 population doublings before senescing. Senescence in keratinocytes was characterised by reduced thymidine incorporation, a change in morphology and the inability of cells to undergo mitosis. This was accompanied by downregulation of cdc2 and E2F-1 mRNA's. In addition, senescing keratinocytes started to express genes such as cornifin, that are specific for squamous differentiation. These changes were similar to those observed in keratinocytes induced to differentiate with phorbol ester or by confluence. E2F-1, cdc2 and cornifin were similarly altered in senescing human mammary epithelial cells. Our data suggest that events regulating senescence may also be linked to squamous differentiation.
Saunders
N A
NA
Cell Biology Section, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709.
Smith
R J
RJ
Jetten
A M
AM
D001483:Base Sequence; D015415:Biomarkers; D001940:Breast / Q000166:cytology / Q000502:physiology; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics; D002454:Cell Differentiation / Q000502:physiology*; D002455:Cell Division / Q000235:genetics*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D055233:Cornified Envelope Proline-Rich Proteins; D015536:Down-Regulation; D004848:Epithelium / Q000502:physiology; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000502:physiology*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D008969:Molecular Sequence Data; D011503:Transglutaminases / Q000096:biosynthesis / Q000235:genetics
D015415:Biomarkers; D055233:Cornified Envelope Proline-Rich Proteins; D008565:Membrane Proteins; D011503:Transglutaminases; D016203:CDC2 Protein Kinase