TY - JOUR
T1 - E2F-1-Induced p53-independent apoptosis in transgenic mice
AU - Holmberg, Christian Henrik
AU - Helin, K.
AU - Sehested, M.
AU - Karlström, Olle
N1 - 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
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
U2 - 10.1038/sj.onc.1201915
DO - 10.1038/sj.onc.1201915
M3 - Journal article
C2 - 9674698
SN - 0950-9232
VL - 17
SP - 143
EP - 155
JO - Oncogene
JF - Oncogene
IS - 2
ER -