AKT1 (E17K) in human solid tumours
| Autor: | Monica Rodolfo, Antonio Marchetti, F Buttitta, Fe Bleeker, Lara Felicioni, M Del Grammastro, Sieger Leenstra, Milo Frattini, Carlo Zanon, Aldo Scarpa, Mattia Barbareschi, Simona Lamba, Mg Sciarrotta, Alberto Bardelli, Luca Cardone |
|---|---|
| Přispěvatelé: | Neurosurgery |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Class I Phosphatidylinositol 3-Kinases Humans *Mutation Neoplasms/*genetics Organ Specificity Phosphatidylinositol 3-Kinases/genetics/physiology Proto-Oncogene Proteins c-akt/*genetics AKT1 Biology medicine.disease_cause Phosphatidylinositol 3-Kinases Germline mutation Neoplasms Genetics medicine Humans cancer Molecular Biology PI3K/AKT/mTOR pathway Mutation Kinase Cancer PIK3CA medicine.disease Hedgehog signaling pathway Organ Specificity embryonic structures Cancer research mutation Carcinogenesis Proto-Oncogene Proteins c-akt |
| Zdroj: | Oncogene, 27(42), 5648-5650. Nature Publishing Group |
| ISSN: | 0950-9232 |
| Popis: | The serine- threonine kinase AKT1 is a central player in the oncogenic pathway controlled by PI3K. Recently, a somatic mutation in AKT1 (E17K) has been detected in breast, colorectal, lung and ovarian cancers. The E17K change results in constitutive AKT1 activation and induces leukaemia in mice. We determined the occurrence of the E17K variant in a panel of 764 tumour samples. These included breast, lung, ovarian, colorectal and pancreatic carcinomas as well as melanomas and glioblastomas. Despite the fact that these tumours are known to bear alterations in genes involved in the PI3K signalling pathway, AKT1(E17K) was detected only in breast (16/273), colorectal (1/88) and lung(1/155) cancers. Within the neoplasms of breast origin, the AKT1(E17K) variant was mutually exclusive with respect to the PIK3CA(E454K) (or H1047R) alleles and was present only in ductal and lobular histotypes. Our results, showing that AKT1 mutations seem to occur in a tissue-specific fashion have basic and clinical implications. First, the activity of mutated AKT1 in oncogenic PI3K signalling could be strictly dependent on the cell and tissue milieu. Second, therapeutic efforts aimed at selective targeting the AKT1(E17K) variant could be effective mainly in specific cancer types |
| Databáze: | OpenAIRE |
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