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Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas
A Bellacosa1, D de Feo, A K Godwin
1Institute of Medical Genetics, Catholic University Medical School, Rome, Italy.
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.
Insights
The AKT2 gene is amplified in ovarian and breast cancers, particularly in aggressive ovarian tumors, indicating a poor prognosis. AKT2 alterations define an independent cancer subset, suggesting a specific role in ovarian cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The AKT2 gene, a human homologue of a viral oncogene, encodes a serine-threonine protein kinase.
- Previous research indicated AKT2 amplification and overexpression in ovarian cancer cell lines and primary tumors.
Purpose of the Study:
- To investigate the frequency and significance of AKT2 gene alterations in a large cohort of ovarian and breast cancer patients.
- To determine if AKT2 alterations are associated with specific cancer subtypes, aggressiveness, or patient prognosis.
Main Methods:
- Southern-blot analysis was used to detect AKT2 gene amplification in ovarian and breast carcinoma samples.
- Northern-blot analysis was employed to assess AKT2 gene expression levels in fresh ovarian carcinomas.
Main Results:
- AKT2 amplification was found in 12.1% of ovarian carcinomas and 2.8% of breast carcinomas.
- Overexpression of AKT2 was observed in some ovarian tumors lacking amplification.
- No AKT2 alterations were detected in benign or borderline ovarian tumors.
- AKT2 amplification was more frequent in undifferentiated tumors and associated with a poor prognosis in ovarian cancer patients.
- AKT2 amplification was independent of MYC and ERBB2 amplification, suggesting distinct oncogenic pathways.
Conclusions:
- The findings suggest a specific role for AKT2 in ovarian oncogenesis and highlight its potential as a marker for aggressive disease.
- AKT2 alterations represent an independent molecular subset in breast and ovarian cancers.
- Further research into AKT2's role could lead to targeted therapeutic strategies for ovarian cancer.