AKT3 drives adenoid cystic carcinoma development in salivary glands.
AKT3 drives adenoid cystic carcinoma development in salivary glands.
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DOI：
10.1002/cam4.1293
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发表时间：
2018-03
期刊：
影响因子：
4
通讯作者：
Moll HP
中科院分区：
文献类型：
--
作者：
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
唾液腺癌是一种侵袭性和疼痛的癌症，但仅占癌症病例的约0.5%的罕见肿瘤类型。涎腺肿瘤具有异质性的组织学和遗传学特征，它们被细分为不同的亚型，其中腺样囊性癌（ACC）是最常见的亚型之一。ACC患者的治疗受到高复发率、肿瘤转移的高可能性以及ACC对化疗的不良反应的困扰。开发靶向治疗的先决条件是深入了解驱动核心癌症途径的遗传信息。在这里，我们开发了一种转基因小鼠模型，以建立临床前模型。目前还没有可用的腺样囊性癌作为罕见疾病实体的小鼠模型来作为通过靶向治疗阻断唾液腺肿瘤的测试系统。基于ACC患者的肿瘤基因组数据，提示PI 3 K-AKT-mTOR通路的激活在分泌腺肿瘤中起关键作用。因此，我们研究了Akt 3表达在肿瘤发生中的作用，并报道了Akt 3过表达导致涎腺ACC 100%失活，而废除转基因Akt 3表达可以逆转表型。总之，我们的研究结果验证了一种新的小鼠模型来研究ACC，并强调了AKT 3在治疗唾液腺患者中的可药用潜力。
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.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
11.2
作者：
Dillon RL;Marcotte R;Hennessy BT;Woodgett JR;Mills GB;Muller WJ
通讯作者：
Muller WJ
DOI：
10.1016/j.bbrc.2008.03.042
发表时间：
2008-05-23
影响因子：
3.1
作者：
Hara, Shingo;Nakashiro, Koh-ichi;Hamakawa, Hiroyuki
通讯作者：
Hamakawa, Hiroyuki
DOI：
10.1038/labinvest.2010.5
发表时间：
2010-04
期刊：
Laboratory investigation; a journal of technical methods and pathology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.6
作者：
Völker HU;Scheich M;Berndt A;Haubitz I;Metzger A;Müller-Hermelink HK;Kämmerer U;Schmidt M
通讯作者：
Schmidt M