Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects

G. De Vita, M. T. Berlingieri, R. Visconti, M. D. Castellone, G. Viglietto, G. Baldassarre, M. Zannini, A. Bellacosa, P. N. Tsichlis, A. Fusco, M. Santoro

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Abstract

The Akt/protein kinase B serine/threonine kinase is a downstream effector of phosphoinositide 3-kinase (P13K). Akt is an important component of mitogenic and antiapoptotic signaling pathways and is implicated in neoplastic transformation. Thyroid cells in culture retain a differentiated phenotype consisting of epithelial cell morphology and the expression of several tissue-specific genes. The survival and proliferation of these cells depend on thyrotropin and a mixture of five additional hormones that includes insulin. The regulation of proliferation and the expression of the thyroid differentiation program are intimately connected processes. As a result, oncogenes that induce hormone-independent proliferation invariably impair the expression of the thyroid-specific differentiation markers. Given that thyrotropin and insulin stimulate Akt activation in thyroid cells, we set out to determine the effects of Akt on thyroid cell proliferation, survival, and differentiation. To this end, we expressed constitutively active myristylated Akt (myrAkt) in PC CI 3 thyroid cells. The myrAkt-expressing cells continued to proliferate, even in the absence of hormones, and they were resistant to programmed cell death induced by starvation. These effects were paralleled by the induction of the G1 cyclins D3 and E and by the inhibition of induction of the proapoptotic Fas, Fas ligand, and BAD genes in starved cells. However, in marked contrast with several other oncogenes, myrAkt did not interfere with the expression of thyroid differentiation functions. These results unveil the existence of an Akttriggered thyroid cell pathway that modulates proliferation and survival without affecting the expression of the thyroid cell differentiated phenotype.

Original languageEnglish
Pages (from-to)3916-3920
Number of pages5
JournalCancer Research
Volume60
Issue number14
Publication statusPublished - Jul 15 2000

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Proto-Oncogene Proteins c-akt
Thyroid Gland
Cell Proliferation
Hormones
Thyrotropin
Oncogenes
Cell Survival
Cyclin D3
Insulin
Phenotype
Cyclin E
Fas Ligand Protein
1-Phosphatidylinositol 4-Kinase
Protein-Serine-Threonine Kinases
Differentiation Antigens
Starvation
Genes
Cell Differentiation
Cell Death
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

De Vita, G., Berlingieri, M. T., Visconti, R., Castellone, M. D., Viglietto, G., Baldassarre, G., ... Santoro, M. (2000). Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects. Cancer Research, 60(14), 3916-3920.

Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects. / De Vita, G.; Berlingieri, M. T.; Visconti, R.; Castellone, M. D.; Viglietto, G.; Baldassarre, G.; Zannini, M.; Bellacosa, A.; Tsichlis, P. N.; Fusco, A.; Santoro, M.

In: Cancer Research, Vol. 60, No. 14, 15.07.2000, p. 3916-3920.

Research output: Contribution to journalArticle

De Vita, G, Berlingieri, MT, Visconti, R, Castellone, MD, Viglietto, G, Baldassarre, G, Zannini, M, Bellacosa, A, Tsichlis, PN, Fusco, A & Santoro, M 2000, 'Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects', Cancer Research, vol. 60, no. 14, pp. 3916-3920.
De Vita, G. ; Berlingieri, M. T. ; Visconti, R. ; Castellone, M. D. ; Viglietto, G. ; Baldassarre, G. ; Zannini, M. ; Bellacosa, A. ; Tsichlis, P. N. ; Fusco, A. ; Santoro, M. / Akt/protein kinase B promotes survival and hormone-independent proliferation of thyroid cells in the absence of dedifferentiating and transforming effects. In: Cancer Research. 2000 ; Vol. 60, No. 14. pp. 3916-3920.
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