Biologic targets for therapeutic intervention in endometrioid endometrial adenocarcinoma and malignant mixed müllerian tumors - 18/08/11
, Rebecca L. Stone, MD a, Miaohou Xu, MD, PhD a, Mary Galgano, MD b, Mark H. Stoler, MD b, Elise N. Everett, MD a, Amir A. Jazaeri, MD a
Reprint requests: Laurel W. Rice, MD, University of Virginia Health System, Box 800712, Charlottesville, VA 22908.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.
Il testo completo di questo articolo è disponibile in PDF.Key words : Malignant mixed müllerian tumor, Endometrial cancer, AKT, mTOR
Mappa
| Supported by the University of Virginia Cancer Center P30 CA44579 and donors. Presented at the Twenty-Fourth Annual Meeting of the American Gynecological and Obstetrical Society, September 29-October 1, 2005, Victoria, British Columbia, Canada. |
Vol 194 - N° 4
P. 1119-1126 - aprile 2006 Ritorno al numero
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