title: Increased expression of genes encoding mitochondrial proteins in papillary thyroid carcinomas.
abstract: To investigate differences in gene expression between normal thyroid tissue and papillary thyroid carcinomas, we performed differential display (DD) polymerase chain reaction (PCR) using total RNA from fresh-frozen surgically removed thyroid specimens. Four DD fragments that were overexpressed in tumor tissue were identified as parts of genes from the mitochondrial genome: nicotinamide adenine dinucleotide (NADH) dehydrogenase 5, adenosine triphosphate (ATP) synthase 6, cytochrome b, and cytochrome c oxidase I. The expression profiles of these genes were confirmed by hybridization using a DNA dot-blot array and radioactively labeled complex cDNA probes generated from tumor (30 biopsies) and nontumor (15 biopsies) total RNA. Cytochrome c oxidase III was also found to be overexpressed in papillary carcinomas, while the nuclear-encoded mitochondrial transcription factor A showed similar mRNA expression levels in tumor and nontumor tissue. Electron microscopy showed increased number and size of mitochondria in papillary carcinomas. Immunohistochemistry using a monoclonal antibody recognizing a nuclear-encoded mitochondrial protein showed positivity in all cases of papillary carcinoma (44 samples), while normal thyroid tissue (34 samples) was negative in all cases except 3, in which there was a weak, focal cytoplasmic staining. We conclude that papillary thyroid carcinomas show increased expression of mitochondrial mRNA and proteins, encoded by nuclear as well as mitochondrial genes.
authors.affiliation: Department of Oncology, Haukeland University Hospital, Bergen, Norway; and Department of Molecular Biology, University of Bergen, Bergen, Norway. dagny.naugen@haukeland.no
authors.forename: Dagny R Faksvåg
authors.initials: DR
authors.lastname: Haugen
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Fluge
authors.forename: Laila J
authors.initials: LJ
authors.lastname: Reigstad
authors.forename: Jan Erik
authors.initials: JE
authors.lastname: Varhaug
authors.forename: Johan R
authors.initials: JR
authors.lastname: Lillehaug
mesh_terms: D002291:Carcinoma, Papillary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018076:DNA, Complementary; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D015335:Molecular Probes; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D018076:DNA, Complementary; D024101:Mitochondrial Proteins; D015335:Molecular Probes