Akt activity in endometrial cancer cells: Regulation of cell survival through cIAP-1

  • Authors:
    • Veronique Gagnon
    • Marie-Eve St-Germain
    • Sophie Parent
    • Eric Asselin
  • View Affiliations

  • Published online on: Monday, September 1, 2003
  • Pages: 803-810
  • DOI: 10.3892/ijo.23.3.803

Abstract

In a number of different cancer including endometrial cancers, tumor suppressor phosphatase tensin homologue (PTEN, a lipid phosphatase) is frequently mutated. PTEN dephosphorylates PI 3-K product, phosphatidylinositol 3,4,5-triphosphate (PIP3), into inactive PIP2 which blocks Akt activation/phosphorylation. In the present study, we have used an endometrial cancer cell line known to possess wild-type PTEN (HEC-1-A) and two mutated inactive PTEN protein cell lines (RL-95-2 and Ishikawa) to investigate importance of PI 3-K/PTEN/Akt survival pathway in endometrial cancers. As hypothesised, results showed high levels of Akt1/2 mRNAs and protein phosphorylation in the two mutated PTEN human endometrial cancer cells. To test the possible involvement of Akt in the regulation of survival factors, Bcl-2, XIAP, cIAP-1 and cIAP-2 expression were measured. cIAP-1 protein expression was high in cells expressing phospho-Akt. XIAP and cIAP-2 protein expression was not influenced by the presence of active Akt. Akt phosphorylation decreased and apoptosis was strongly increased in mutated PTEN human endometrial cancer cells in the presence of PI 3-K inhibitor (Wortmannin) which was accompanied by a down-regulation of cIAP-1 protein. Wortmannin had no effect on wild-type PTEN HEC-1-A cell line. Although, Bcl-2 expression was strongly expressed in mutated-PTEN cells, expression remained stable in the presence of Wortmannin suggesting that Bcl-2 is not regulated by Akt. Overexpression of Akt using a constitutively active Akt expression vector resulted in an up-regulation of cIAP-1 expression. These results suggest a pivotal role of Akt in the regulation of endometrial cancer cell survival through the up-regulation of a specific inhibitor of apoptosis protein.
Journal Cover

September 2003
Volume 23 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Gagnon, V., St-Germain, M., Parent, S., & Asselin, E. (2003). Akt activity in endometrial cancer cells: Regulation of cell survival through cIAP-1. International Journal of Oncology, 23(3), 803-810.
MLA
Gagnon, St-Germain, Parent, and Eric Asselin. "Akt activity in endometrial cancer cells: Regulation of cell survival through cIAP-1." International Journal of Oncology International Journal of Oncology 23.3 (2003): 803-810.
Chicago
Gagnon, St-Germain, Parent, and Eric Asselin. "Akt activity in endometrial cancer cells: Regulation of cell survival through cIAP-1." International Journal of Oncology International Journal of Oncology 23 no. 3 (2003): 803-810.