E2F-1-Induced p53-independent apoptosis in transgenic mice

Christian Henrik Holmberg, K. Helin, M. Sehested, Olle Karlström

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    Abstract

    The E2F transcription factors are key targets for the retinoblastoma protein, pRB. By inactivation of E2Fs, pRB prevents progression to the S phase. To test proliferative functions of E2F, we generated transgenic mice expressing human E2F-1 and/or human DP-1. When the hydroxymethyl glutaryl coenzyme A reductase promoter was used to express DP-1, overexpression occurred in a variety of tissues and did not confer phenotypic changes. In contrast, expression of E2F-1 from the same promoter was obtained only in testicles, in which E2F-1 overexpression caused atrophy and sterility through a process involving increased apoptosis in the germinal epithelium. This effect was potentiated by simultaneous overexpression of DP-1. Testicular atrophy as a result of overexpression of E2F-1 and DP-1 is independent of functional p53, since p53-nullizygous transgenic mice overexpressing E2F-1 and DP-1 also suffered testicular atrophy.
    Original languageEnglish
    JournalOncogene
    Volume17
    Issue number2
    Pages (from-to)143-155
    Number of pages12
    ISSN0950-9232
    DOIs
    Publication statusPublished - 1998

    Bibliographical note

    Keywords: Animals; Apoptosis; Atrophy; Carrier Proteins; Cell Cycle Proteins; DNA-Binding Proteins; E2F Transcription Factors; E2F1 Transcription Factor; Humans; Infertility, Male; Male; Mice; Mice, Transgenic; Testis; Transcription Factor DP1; Transcription Factors; Tumor Suppressor Protein p53

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