National Cancer Institute
Mammalian development requires the presence of both parental genomes due to genomic imprinting. Primary mouse embryonic fibroblast (MEF) lines, in which their entire genome is exclusively maternal (parthenogenetic) or paternal (androgenetic), appropriately and stably express known imprinted genes but have dramatically contrasting patterns of proliferation. Androgenetic proliferation is more rapid, has a shorter cell cycle, and the cells show increased tumor formation compared to biparental MEFs. Parthenogenetic fibroblasts reach a lower saturation density, senesce and die. The maternally expressed imprinted genes 57Kip2 and M6p/Igf2r retard proliferation and reduce the viability of the parthenogenetic lines. In contrast, the paternally expressed growth factor Igf2 is essential for the long-term proliferation of all three parental genotypes. Increasing Igf2 expression in primary MEFs stimulates proliferation and results in the rapid induction of tumors. Parental genomes are each endowed with a unique set of intrinsic growth characteristics, one of which is a critical role in regulating Igf2 as a potential factor in oncogenesis.