Abstract
Objective: The purpose of this study was to investigate the AKT signaling cascade in endometrial cancers and to assess its therapeutic potential. Study design: Western blotting and immunohistochemistry were used to investigate the expression of estrogen receptor, progesterone receptor, HER2, AKT, and 4EBP1 proteins in 27 atrophic endometria, 31 grade 1 and 24 grade 3 endometrioid endometrial cancers, and 19 malignant mixed müllerian tumors. Inhibition of the AKT signaling cascade was investigated in cell lines. Results: Malignant mixed müllerian tumors and grade 3 endometrioid endometrial cancers demonstrated higher levels of AKT and 4EBP1 activation and hormone receptor loss compared with grade 1 endometrioid endometrial cancers and atrophic samples. HER2 over-expression was identified most often in grade 3 tumors without gene amplification. In endometrial cancer cell-lines, AKT cascade inhibitors decreased cell proliferation by apoptosis and cell cycle arrest. Conclusion: AKT cascade activation in grade 3 endometrioid endometrial cancers and malignant mixed müllerian tumors is a novel finding. Apoptosis and growth arrest that results from AKT inhibition expose opportunities for therapeutic intervention.
Original language | English (US) |
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Pages (from-to) | 1119-1126 |
Number of pages | 8 |
Journal | American journal of obstetrics and gynecology |
Volume | 194 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2006 |
Externally published | Yes |
Keywords
- AKT
- Endometrial cancer
- Malignant mixed müllerian tumor
- mTOR
ASJC Scopus subject areas
- Obstetrics and Gynecology