DIFFERENTIAL EXPRESSION OF A TUMOR-NECROSIS-FACTOR RECEPTOR-RELATED TRANSCRIPT IN GESTATIONAL TROPHOBLASTIC DISEASES IN WOMEN

Gestational trophoblastic diseases comprise a group of interrelated ne oplasms, including complete hydatidiform mole (CHM), persistent gestat ional trophoblastic tumor (GTT), and choriocarcinoma. To better define the molecular features of these diseases, a CHM cDNA library was cons tructed and a novel cDNA sequence, named CHMS-1, was isolated by diffe rential screening. The CHMS-1 sequence showed a 62% homology with the tumor necrosis factor receptor (TNF-R2) cDNA, and its amino acid deduc ed sequence shared a high level of homology with the ''death domain'' region found in various proteins, including two members of the TNF rec eptor superfamily, the TNF-R1 and Fas; We also determined the CHMS-1, TNF-R1, and TNF-R2 expression patterns among different CHM tissues and cell lines of trophoblastic (JEG-3) and nontrophoblastic (HeLa and CO S-7) origin. Our results indicated that the CHMS-1 transcript is highl y expressed in CHM in comparison with both normal early and term place nta and that it exhibits an expression profile identical to that of TN F-R1. Furthermore, the CHMS-1 transcript was undetectable in CHM-deriv ed GTT and in the human choriocarcinoma-derived JEG-3 cells, suggestin g that its expression is down-regulated in the malignant transformatio n of trophoblast. The presence of a potential ''death domain'' in CHMS -1, together with its high expression level in CHM, strongly suggests that the CHMS-1 gene encodes a protein that might be involved in tumor regression processes occurring at later stages of molar development.