PTEN is among the most frequently mutated and deleted tumor suppressor genes in many malignancies, including breast cancer. An alternatively translated long form of PTEN, termed PTEN-L, has divergent functionality from PTEN, although its function at the organism level has not been studied. Here, we report a knockout mouse with specific ablation of PTEN-L expression but intact expression of PTEN. These mice display mammary ductal hyperplasia characterized by increased luminal growth and increased numbers of macrophages in the surrounding stroma. Macrophages are particularly affected by PTEN-L loss, with significant changes to their secretomes and functional deficiencies in clearing bacterial infections, consistent with a shift toward an M2-like polarization. Overall, these findings demonstrate that PTEN-L has unique functions in regulating mammary epithelial growth and macrophage functionality that are independent of canonical PTEN.

Citation Format: Andrew L. Wolfe, Benjamin D. Hopkins, Sebastián A. Riquelme, Kipyegon Kitur, Sait Ozturk, Kyeongah Kang, Romain Remark, Adeeb Rahman, Chyuan-Sheng Lin, Miriam Merad, Matthias Szabolcs, Shu-Hsia Chen, Alice Prince, Ramon Parsons. PTEN-L regulates epithelial growth and macrophage function [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 334. doi:10.1158/1538-7445.AM2017-334