AKT3 drives adenoid cystic carcinoma development in salivary glands

Katalin Zboray, Julian Mohrherr, Patricia Stiedl, Klemens Pranz, Laura Wandruszka, Beatrice Grabner, Robert Eferl, Richard Moriggl, Dagmar Stoiber, Kazuhito Sakamoto, Kay Uwe Wagner, Helmut Popper, Emilio Casanova, Herwig P. Moll

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 PI3K-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 AKT3 in the treatment of salivary gland patients.

Original languageEnglish (US)
Pages (from-to)445-453
Number of pages9
JournalCancer Medicine
Volume7
Issue number2
DOIs
StatePublished - Feb 1 2018

Fingerprint

Adenoid Cystic Carcinoma
Salivary Glands
Neoplasms
Salivary Gland Neoplasms
Glandular and Epithelial Neoplasms
Penetrance
Therapeutics
Rare Diseases
Phosphatidylinositol 3-Kinases
Transgenic Mice
Carcinogenesis
Phenotype
Recurrence
Drug Therapy

Keywords

  • AKT3
  • Adenoid cystic carcinoma
  • MMTV-tTA mouse model
  • oncogene addiction
  • salivary gland cancer

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

Zboray, K., Mohrherr, J., Stiedl, P., Pranz, K., Wandruszka, L., Grabner, B., ... Moll, H. P. (2018). AKT3 drives adenoid cystic carcinoma development in salivary glands. Cancer Medicine, 7(2), 445-453. https://doi.org/10.1002/cam4.1293

AKT3 drives adenoid cystic carcinoma development in salivary glands. / Zboray, Katalin; Mohrherr, Julian; Stiedl, Patricia; Pranz, Klemens; Wandruszka, Laura; Grabner, Beatrice; Eferl, Robert; Moriggl, Richard; Stoiber, Dagmar; Sakamoto, Kazuhito; Wagner, Kay Uwe; Popper, Helmut; Casanova, Emilio; Moll, Herwig P.

In: Cancer Medicine, Vol. 7, No. 2, 01.02.2018, p. 445-453.

Research output: Contribution to journalArticle

Zboray, K, Mohrherr, J, Stiedl, P, Pranz, K, Wandruszka, L, Grabner, B, Eferl, R, Moriggl, R, Stoiber, D, Sakamoto, K, Wagner, KU, Popper, H, Casanova, E & Moll, HP 2018, 'AKT3 drives adenoid cystic carcinoma development in salivary glands', Cancer Medicine, vol. 7, no. 2, pp. 445-453. https://doi.org/10.1002/cam4.1293
Zboray K, Mohrherr J, Stiedl P, Pranz K, Wandruszka L, Grabner B et al. AKT3 drives adenoid cystic carcinoma development in salivary glands. Cancer Medicine. 2018 Feb 1;7(2):445-453. https://doi.org/10.1002/cam4.1293
Zboray, Katalin ; Mohrherr, Julian ; Stiedl, Patricia ; Pranz, Klemens ; Wandruszka, Laura ; Grabner, Beatrice ; Eferl, Robert ; Moriggl, Richard ; Stoiber, Dagmar ; Sakamoto, Kazuhito ; Wagner, Kay Uwe ; Popper, Helmut ; Casanova, Emilio ; Moll, Herwig P. / AKT3 drives adenoid cystic carcinoma development in salivary glands. In: Cancer Medicine. 2018 ; Vol. 7, No. 2. pp. 445-453.
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