Altered mitochondrial gene expression in human gestational trophoblastic diseases

To assess the molecular basis of phenotypic alterations present in the gest ational trophoblastic diseases (GTDs) and to identify genes whose expressio n is specifically associated with these placental proliferative disorders w e performed differential display (DD) techniques. This strategy resulted in the isolation of four mitochondrial transcripts downregulated in benign, a s well as in malignant, trophoblastic diseases encoding the cytochrome oxid ase subunit I (COS I), the ATPase subunit 6, the 12S ribosomal RNA (12S rRN A) and the transfer RNA for phenylalanine (tRNA(Phe)). This expression pattern was confirmed by Northern blot in normal early plac enta (NEP), complete hydatidiform mole (CHM), persistent gestational tropho blastic disease (PGTD) and the human choriocarcinoma derived cell line JEG- 3. Quantification of mitochondrial DNA by dot blot indicated that these cha nges in expression were not associated with a significant alteration in the number of mitochondrial genome. In addition, a reduction in the mitochondr ial transcription factor A (mtTFA) mRNA level was observed in benign as wel l as in malignant trophoblastic diseases in correlation with the decrease i n the mitochondrial transcript levels. Furthermore, Western blot analysis f or COX-I showed a close parallelism with the expression level of the cognat e RNA. Taken together, these data demonstrate that a significant change in mitochondrial transcription is associated with the phenotypic alteration pr esent in GTDs. (C) 2001 Harcourt Publishers Ltd.