Tumor heterogeneity, aggressiveness, and immune cell composition in a novel syngeneic PSA-targeted Pten knockout mouse prostate cancer (MuCaP) model.

Background: Prostate cancer is recognized as a heterogeneous disease demanding appropriate preclinical models that reflect tumor complexity. Previously, we established the PSA-Cre;PtenLoxP/LoxP genetic engineered mouse model (GEMM) for prostate cancer reflecting the various stages of tumor development. Prostate tumors in this Pten KO model slowly develop, requiring more than 10 months.

Spatial aspects of oncogenic signalling determine the response to combination therapy in slice explants from Kras-driven lung tumours.

A key question in precision medicine is how functional heterogeneity in solid tumours informs therapeutic sensitivity. We demonstrate that spatial characteristics of oncogenic signalling and therapy response can be modelled in precision-cut slices from Kras-driven non-small-cell lung cancer with varying histopathologies. Unexpectedly, profiling of in situ tumours demonstrated that signalling stratifies mostly according to histopathology, showing enhanced AKT and SRC activity in adenosquamous carcinoma, and mitogen-activated protein kinase (MAPK) activity in adenocarcinoma.

Characterization of Heterogeneous Prostate Tumors in Targeted Pten Knockout Mice.

Previously, we generated a preclinical mouse prostate tumor model based on PSA-Cre driven inactivation of Pten. In this model homogeneous hyperplastic prostates (4-5m) developed at older age (>10m) into tumors. Here, we describe the molecular and histological characterization of the tumors in order to better understand the processes that are associated with prostate tumorigenesis in this targeted mouse Pten knockout model.

PI3K/Akt signaling regulates p27(kip1) expression via Skp2 in PC3 and DU145 prostate cancer cells, but is not a major factor in p27(kip1) regulation in LNCaP and PC346 cells.

Background: We compared the involvement of PI3K/PTEN/Akt signaling in the regulation of the cell-cycle regulator p27(kip1) and investigated the mechanism of PI3K/PTEN/Akt modulation of p27(kip1) in the prostate cancer cell lines LNCaP, PC346, PC3, and DU145.

Methods: PI3K/PTEN/Akt signaling was manipulated by wortmannin or specific siRNA. The effects on PI3K/Akt downstream effectors and p27(kip1) expression were monitored on RNA and protein levels.