Altered mitochondrial gene expression in human gestational trophoblastic diseases.
To assess the molecular basis of phenotypic alterations present in the gestational trophoblastic diseases (GTDs) and to identify genes whose expression is specifically associated with these placental proliferative disorders we performed differential display (DD) techniques. This strategy resulted in the isolation of four mitochondrial transcripts downregulated in benign, as well as in malignant, trophoblastic diseases encoding the cytochrome oxidase subunit I (COX I), the ATPase subunit 6, the 12S ribosomal RNA (12S rRNA) and the transfer RNA for phenylalanine (tRNA(Phe)). This expression pattern was confirmed by Northern blot in normal early placenta (NEP), complete hydatidiform mole (CHM), persistent gestational trophoblastic disease (PGTD) and the human choriocarcinoma derived cell line JEG-3. Quantification of mitochondrial DNA by dot blot indicated that these changes in expression were not associated with a significant alteration in the number of mitochondrial genome. In addition, a reduction in the mitochondrial transcription factor A (mtTFA) mRNA level was observed in benign as well as in malignant trophoblastic diseases in correlation with the decrease in the mitochondrial transcript levels. Furthermore, Western blot analysis for COX-I showed a close parallelism with the expression level of the cognate RNA. Taken together, these data demonstrate that a significant change in mitochondrial transcription is associated with the phenotypic alteration present in GTDs.
Durand
S
S
Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Pabellón Argentina, Ala Oeste, Ciudad Universitaria, 5000 Córdoba, Argentina.
Dumur
C
C
Flury
A
A
Abadie
P
P
Patrito
L
L
Podhajcer
O
O
Genti-Raimondi
S
S
D000251:Adenosine Triphosphatases / Q000235:genetics; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002822:Choriocarcinoma / Q000235:genetics*; D003001:Cloning, Molecular; D004272:DNA, Mitochondrial / Q000737:chemistry / Q000235:genetics*; D003576:Electron Transport Complex IV / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D006828:Hydatidiform Mole / Q000235:genetics*; D007527:Isoenzymes; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger / Q000032:analysis; D012360:RNA, Transfer, Phe / Q000235:genetics; D017422:Sequence Analysis, DNA; D017385:Sequence Homology; D014328:Trophoblastic Neoplasms / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms / Q000235:genetics*
D004272:DNA, Mitochondrial; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D012360:RNA, Transfer, Phe; D011451:Prostaglandin-Endoperoxide Synthases; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases