Increased expression of genes encoding mitochondrial proteins in papillary thyroid carcinomas.
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.
Haugen
Dagny R Faksvåg
DR
Department of Oncology, Haukeland University Hospital, Bergen, Norway; and Department of Molecular Biology, University of Bergen, Bergen, Norway. dagny.naugen@haukeland.no
Fluge
Øystein
Ø
Reigstad
Laila J
LJ
Varhaug
Jan Erik
JE
Lillehaug
Johan R
JR
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
D018076:DNA, Complementary; D024101:Mitochondrial Proteins; D015335:Molecular Probes