Cooperation Between Pten and Smad4 in Murine Salivary Gland Tumor Formation and Progression

• DOI: 10.1016/j.neo.2018.05.009
• Publication Date: 2018-06-28T00:02:30Z
• Authors: Yu Cao; Han Liu; Liwei Gao; Ling Lu; Li Du; Han Bai; Jiang Li; Sherif Said; Xiao-Jing Wang; John Song; Natalie Serkova; Minjie Wei; Jing Xiao; Shi-Long Lu
• Keywords: Adenoid Cystic Carcinoma; Keratin 5; Tumor progression

Salivary gland tumor (SGT) is a rare type, which exhibits broad-spectrum phenotypic, biological, and clinical heterogeneity. Currently, the molecular mechanisms that cause SGT pathogenesis remain poorly understood. A lack of animal models faithfully recapitulate naturally occurring process human SGTs has hampered research progress on this field. In report, we developed an inducible keratin 5-driven conditional knockout mouse model to delete gene(s) interest in murine salivary upon local RU486 delivery. We have deleted two major suppressors, Pten, negative regulator PI3K pathway, Smad4, central signaling mediator TGFβ gland. Our results shown deletion either Pten or Smad4 resulted pleomorphic adenomas, most common patients. Deletion both several malignancies, with adenoid cystic carcinoma (SACC) being frequently seen. Molecular characterization showed SACC exhibited mTOR activation TGFβ1 overexpression. Examination samples revealed loss samples, particularly aggressive solid form, correlated survival patients, highlighting relevance models. summary, our offer significant insight into synergistic role SGT, providing rationale for targeting and/or control formation progression.