Altered mitochondrial expression in gestational trophoblastic diseases (GTDs)

DURAND E.S.; DUMUR C.; FLURY A.; ABADIE P.; PATRITO L.C.; PODHAJCER O. ; GENTI-RAIMONDI S.

Buenos Aires

Simposio; Common Themes in Transcription and RNA Processing; 1999

International Centre for Genetic Engineering and Biotechnology (Italy), Agencia Nacional de Promoción de Ciencia y Tecnología, Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular, y Universidad de Buenos Aires (Argentina)

GTDs comprise a heterogeneous group of interrelated lesions which are characterized by an abnormal proliferation of different types of trophoblastic epithelium. In an attempt to asses the molecular basis of phenotypic alterations present in the GTDs and to identify those genes whose expression is specifically associated with the neoplastic phenotype, we compared by differential display the pattern of gene expression among four trophoblastic tissues. This strategy result in the isolation of two mitochondrial transcripts down-regulated in benign as well as in malignant trophoblastic diseases encoding cytochrome oxidase subunit I (COX I) and pre-tRNAPhe. This expression pattern was confirmed by Northern blot in normal term placenta (NTP), normal early placenta (NEP), two complete hydatidiform moles (CHM), persistent gestational trophoblastic disease (PGTD) and JEG-3 cell line. Quantification of COX I subunit I DNA by dot indicates that these changes in expression were not associated with significant alteration in the number of mitochondrial genome. In addition, a reduction in mt transcription factor A RNA level was observed in benign as well as in malignant trophoblastic diseases in correlation with a decreased mitochondrial transcript levels. Unexpectedly, the immunohistochemical staining of hCOX-I found in malignant trophoblastic diseases was higher than those determined in benign trophoblastic tissues and no parallelism with its mitochondrial transcript level was observed. Our findings suggest that both regulation of mtRNAs stabilitiy and/or translation occur in malignant trophoblastic diseases in order to compensate for the decreased mtDNA transcription. This work was supported by grants from CONICET, FONCyT and SECyT.