APE/Ref-1 is increased in nuclear fractions of human thyroid hyperfunctioning nodules.
Apurinic/apyrimidinic endonuclease APE/Ref-1 is a multifunctional protein provided with DNA repair, transcription-factor regulation and anti-apoptotic activities. We have previously reported that, in thyroid cells, TSH regulates both the synthesis and nuclear translocation of APE/Ref-1. We have also shown that nuclear levels of this protein are reduced both in thyroid carcinoma tissues and cell lines. In the present study, APE/Ref-1 expression and cellular localization were analysed by Western blot in hyperfunctioning thyroid nodules from patients with toxic adenoma and/or toxic multinodular goiter. The total content of APE/Ref-1 protein was increased in the majority of the hyperfunctioning tissues with respect to normal adjacent tissue. There was also an increase in the nuclear levels of APE/Ref-1, suggesting enhanced cytoplasm-to-nucleus translocation of the protein in addition to its increased rate of synthesis. These results demonstrate that the phenomenon of nuclear translocation of APE/Ref-1 hypothesized on the basis of cell culture experiments does actually occur in vivo. Together with previous observations in thyroid carcinomas and tumoral cell lines, our findings suggest a two-stage model of APE/Ref-1 behaviour during malignant thyrocyte transformation: an early stage characterized by simple hyperplasia and upregulation of APE/Ref-1 in the nuclear compartment of the cell and a later stage in which nuclear levels of the protein drop to below-normal levels as the cell becomes progressively undifferentiated.
Russo
D
D
Dipartimento di Scienze Farmacobiologiche, University of Catanzaro, Catanzaro, Italy.
Celano
M
M
Bulotta
S
S
Bruno
R
R
Arturi
F
F
Giannasio
P
P
Filetti
S
S
Damante
G
G
Tell
G
G
D021581:Active Transport, Cell Nucleus; D000236:Adenoma / Q000473:pathology; D000368:Aged; D019757:Carbon-Oxygen Lyases / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D002467:Cell Nucleus / Q000201:enzymology; D002471:Cell Transformation, Neoplastic / Q000737:chemistry; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005260:Female; D006044:Goiter, Nodular / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D021381:Protein Transport; D016606:Thyroid Nodule / Q000201:enzymology / Q000473:pathology*; D015854:Up-Regulation
D019757:Carbon-Oxygen Lyases; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase