Abstract:
:Phosphoinositide 3-kinases (PI3K) are key molecular players in male fertility. However, the specific roles of different p110 PI3K catalytic subunits within the spermatogenic lineage have not been characterized so far. Herein, we report that male mice expressing a catalytically inactive p110beta develop testicular hypotrophy and impaired spermatogenesis, leading to a phenotype of oligo-azoospermia and defective fertility. The examination of testes from p110beta-defective tubules demonstrates a widespread loss in spermatogenic cells, due to defective proliferation and survival of pre- and postmeiotic cells. In particular, p110beta is crucially needed in c-Kit-mediated spermatogonial expansion, as c-Kit-positive cells are lost in the adult testis and activation of Akt by SCF is blocked by a p110beta inhibitor. These data establish that activation of the p110beta PI3K isoform by c-Kit is required during spermatogenesis, thus opening the way to new treatments for c-Kit positive testicular cancers.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Ciraolo E,Morello F,Hobbs RM,Wolf F,Marone R,Iezzi M,Lu X,Mengozzi G,Altruda F,Sorba G,Guan K,Pandolfi PP,Wymann MP,Hirsch Edoi
10.1091/mbc.e09-08-0744subject
Has Abstractpub_date
2010-03-01 00:00:00pages
704-11issue
5eissn
1059-1524issn
1939-4586pii
E09-08-0744journal_volume
21pub_type
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