Misexpression of cyclin D1 in embryonic germ cells promotes testicular teratoma initiation

Cell Cycle
Denise G LanzaJason D Heaney

Abstract

Testicular teratomas result from anomalies in embryonic germ cell development. In the 129 family of inbred mouse strains, teratomas arise during the same developmental period that male germ cells normally enter G1/G0 mitotic arrest and female germ cells initiate meiosis (the mitotic:meiotic switch). Dysregulation of this switch associates with teratoma susceptibility and involves three germ cell developmental abnormalities seemingly critical for tumor initiation: delayed G1/G0 mitotic arrest, retention of pluripotency, and misexpression of genes normally restricted to embryonic female and adult male germ cells. One misexpressed gene, cyclin D1 (Ccnd1), is a known regulator of cell cycle progression and an oncogene in many tissues. Here, we investigated whether Ccnd1 misexpression in embryonic germ cells is a determinant of teratoma susceptibility in mice. We found that CCND1 localizes to teratoma-susceptible germ cells that fail to enter G1/G0 arrest during the mitotic:meiotic switch and is the only D-type cyclin misexpressed during this critical developmental time frame. We discovered that Ccnd1 deficiency in teratoma-susceptible mice significantly reduced teratoma incidence and suppressed the germ cell proliferation and pluri...Continue Reading

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Citations

Jan 13, 2017·Molecular Reproduction and Development·Helen K SalzJason D Heaney
Apr 5, 2017·Stem Cells International·Gregory M Kelly, Mohamed I Gatie
Jan 31, 2018·Biology Open·Wei GuYasuhisa Matsui
Apr 30, 2021·Development·Nicholas J WebsterJason D Heaney
Jun 30, 2021·Andrology·Jiandong SunShie Wang

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Methods Mentioned

BETA
transgenic
Confocal microscopy
fluorescence-activated cell sorting
FACS
Confocal
PCR
genotyping
fluorescence-activated
dissection

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