Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas

International Journal of Cancer - Tập 64 Số 4 - Trang 280-285 - 1995
Alfonso Bellacosa1,2,3,4,5, Daniela De Feo4, Andrew K. Godwin6, Daphne W. Bell6, Jin Q. Cheng6, Deborah A. Altomare6, Minghong Wan7, Louis Dubeau7, Giovanni Scambia8, Valeria Masciullo8, Gabriella Ferrandina8, Pierluigi Benedetti Panici8, Salvatore Mancuso8, Giovanni Neri4, Joseph R. Testa1,6,2,3,5
1Alfonso Bellacosa, Institute of Medical Genetics, L. go F. Vito 1, 00168 Rome, Italy
2Fax: 1 215 7282741
3Fax: 39 6 3050031
4Institutes of Medical Genetics, Rome, Italy
5Joseph R. Testa, Department of Medical Oncology, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
6Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
7Kenneth Norris Jr. Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA
8Obstetrics and Gynecology, Catholic University Medical School, Rome, Italy

Tóm tắt

Abstract

The AKT2 gene is one of the human homologues of v‐akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, which codes for a serine‐threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large‐scale, multicenter study of AKT2 alterations in ovarian and breast cancer. Southern‐blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern‐blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto‐oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness. © 1995 Wiley‐Liss, Inc.

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International Journal of Cancer

Tập 64 Số 4

280-285

Thông tin tác giả