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Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer
  1. V Vasko1,2,3,4,
  2. M Saji1,2,
  3. E Hardy2,
  4. M Kruhlak5,
  5. A Larin3,
  6. V Savchenko3,
  7. M Miyakawa6,
  8. O Isozaki6,
  9. H Murakami6,
  10. T Tsushima6,
  11. K D Burman2,
  12. C De Micco4,
  13. M D Ringel1,2
  1. 1Ohio State University School of Medicine and Arthur G. James Cancer Center, Columbus, OH, USA
  2. 2MedStar Research Institute/Washington Hospital Center, Washington DC, USA
  3. 3Center for Endocrine Surgery, Kiev, Ukraine
  4. 4INSERM U555, Mediterranean University, Marseilles, France
  5. 5National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
  6. 6Tokyo Women’s Medical University, Tokyo, Japan
  1. Correspondence to:
 Dr M D Ringel
 Associate Professor of Medicine, Divisions of Endocrinology and Oncology, 455D McCambell Hall, 1581 Dodd Drive, Columbus, OH 43210, USA;


Introduction: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden’s syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression.

Methods: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples.

Results: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition.

Discussion: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.

  • Metastases
  • vascular invasion
  • Ret oncogene
  • Ras oncogene
  • cell migration
  • AA, atypical adenoma
  • FA, follicular adenoma
  • FC, follicular carcinoma
  • FVPC, follicular variant of papillary carcinomas
  • IGF, insulin-like growth factor
  • MMP, matrix metalloproteinase
  • PC, papillary carcinomas

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