E2F-1-induced p53-independent apoptosis in transgenic mice - PubMed (original) (raw)

. 1998 Jul 16;17(2):143-55.

doi: 10.1038/sj.onc.1201915.

Affiliations

• PMID: 9674698
• DOI: 10.1038/sj.onc.1201915

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

C Holmberg et al. Oncogene. 1998.

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.

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