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

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

doi:10.1038/sj.onc.1201915

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

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

111 Citations (Scopus)

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 language	English
Journal	Oncogene
Volume	17
Issue number	2
Pages (from-to)	143-155
Number of pages	12
ISSN	0950-9232
DOIs	https://doi.org/10.1038/sj.onc.1201915
Publication status	Published - 1998

Access to Document

10.1038/sj.onc.1201915

Cite this

@article{c876f7d074c911dbbee902004c4f4f50,

title = "E2F-1-Induced p53-independent apoptosis in transgenic mice",

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.",

author = "Holmberg, {Christian Henrik} and K. Helin and M. Sehested and Olle Karlstr{\"o}m",

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",

year = "1998",

doi = "10.1038/sj.onc.1201915",

language = "English",

volume = "17",

pages = "143--155",

journal = "Oncogene",

issn = "0950-9232",

publisher = "nature publishing group",

number = "2",

}

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 -

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

Abstract

Access to Document

Fingerprint

Cite this