A new death domain associated with gestational trophoblastic diseases induces apoptosis in distinct cell types

Gestational trophoblastic diseases, like the complete hydatidiform mole (CH M), are a group of human interrelated neoplasms whose ethiology and progres sion is poorly understood at the molecular level. We have previously report ed the cloning and expression of a new tumor necrosis factor receptor (TNF- R) related transcript, named CHMS-1 that encodes a potential death domain. Here we show that ectopic expression of the putative CHMS-1 death domain sp ecifically induced apoptosis in a dose-dependent manner, in trophoblastic ( JEG-3) and non-trophoblastic (COS-7) cells. We also investigated the expres sion of apoptosis-related molecules such as Bcl-2 and p53 and demonstrated that Bcl-2 is repressed in CHM while p53 is overexpressed in CHM compared w ith persistent gestational trophoblastic tumors. Altogether, these data ind icate that the CHMS-1 death domain is able to trigger apoptosis, thus sugge sting that this new entity might be an important inducer of molar regressio n mechanisms in women.