Ovarian follicular growth and atresia: The relationship between cell proliferation and survival1,2

The Forkhead transcription factors AFX, FKHR and FKHR-L1 are orthologues of DAF-16, a Forkhead factor that regulates longevity in Caenorhabditis elegans. Here we show that overexpression of these Forkhead transcription factors causes growth suppression in a variety of cell lines, including a Ras-transformed cell line and a cell line lacking the tumour suppressor PTEN. Expression of AFX blocks cell-cycle progression at phase G1, independent of functional retinoblastoma protein (pRb) but dependent on the cell-cycle inhibitor p27kip1. Indeed, AFX transcriptionally activates p27kip1, resulting in increased protein levels. We conclude that AFX-like proteins are involved in cell-cycle regulation and that inactivation of these proteins is an important step in oncogenic transformation.

Programmed cell death claims up to 99.9% of the cells in the mammalian female germ line, which eventually drives irreversible infertility and ovarian failure - the menopause in humans. New insights into the mechanisms that underlie germ-cell apoptosis have been provided by the study of oocyte death in lower organisms and in genetically manipulated mice that lack apoptosis-regulatory proteins. With new therapeutic tools to control fertility, oocyte quality and ovarian lifespan on the horizon, understanding how and why the female body creates, only to delete, so many germ cells is imperative.