Open AccessAKT 3 drives adenoid cystic carcinoma development in salivary glands
Author(s) -
Zboray Katalin,
Mohrherr Julian,
Stiedl Patricia,
Pranz Klemens,
Wandruszka Laura,
Grabner Beatrice,
Eferl Robert,
Moriggl Richard,
Stoiber Dagmar,
Sakamoto Kazuhito,
Wagner KayUwe,
Popper Helmut,
Casanova Emilio,
Moll Herwig P.
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1293
Subject(s) - adenoid cystic carcinoma , salivary gland , salivary gland cancer , cancer research , cancer , pi3k/akt/mtor pathway , adenoid , carcinogenesis , medicine , genetically modified mouse , pathology , biology , transgene , carcinoma , signal transduction , gene , genetics
Salivary gland cancer is an aggressive and painful cancer, but a rare tumor type accounting for only ~0.5% of cancer cases. Tumors of the salivary gland exhibit heterogeneous histologic and genetic features and they are subdivided into different subtypes, with adenoid cystic carcinomas ( ACC ) being one of the most abundant. Treatment of ACC patients is afflicted by high recurrence rates, the high potential of the tumors to metastasize, as well as the poor response of ACC to chemotherapy. A prerequisite for the development of targeted therapies is insightful genetic information for driver core cancer pathways. Here, we developed a transgenic mouse model toward establishment of a preclinical model. There is currently no available mouse model for adenoid cystic carcinomas as a rare disease entity to serve as a test system to block salivary gland tumors with targeted therapy. Based on tumor genomic data of ACC patients, a key role for the activation of the PI 3K‐ AKT ‐ mTOR pathway was suggested in tumors of secretory glands. Therefore, we investigated the role of Akt3 expression in tumorigenesis and report that Akt3 overexpression results in ACC of salivary glands with 100% penetrance, while abrogation of transgenic Akt3 expression could revert the phenotype. In summary, our findings validate a novel mouse model to study ACC and highlight the druggable potential of AKT 3 in the treatment of salivary gland patients.