Abstract A41: Inhibition of Lkb1 in cultured embryonic pancreas destabilizes tissue architecture to generate precancerous-like lesions

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 19_Supplement; p. A41
• Main Authors: Lo, Bryan, Viotti, Manuel, Strasser, Geraldine, Mellman, Ira
• Format: Journal Article
• Language: English
• Published: 01.10.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.FBCR13-A41

Abstract The tumor suppressor Lkb1 is a regulator of cellular energy, proliferation, and polarity, yet the mechanism by which it controls tissue morphogenesis or cancer remains poorly defined. By culturing embryonic tissues from mice harboring a mutant Lkb1 that can be rapidly inhibited, we have previously shown that acute loss of Lkb1 results in destabilized tissue architecture and the formation of highly dynamic pancreatic cysts (Lo et al, JCB 2012). Remarkably, the pancreatic cysts evolve within a few days into precancerous-like lesions that we now demonstrate to have a transcriptional profile that is strikingly similar to those reported for mouse and human PanINs (Pancreatic Intraepithelial Neoplasias). Utilizing fluorescence activated cell sorting, we have begun to track gene expression signatures associated with canonical signaling pathways in both single cells and subsets of cells from the embryonic explants. Since our experimental system offers precise temporal control and accessibility to manipulation within a tissue context, we are able to gain unprecedented insight into the earliest events in pancreatic oncogenesis. Citation Format: Bryan Lo, Manuel Viotti, Geraldine Strasser, Ira Mellman. Inhibition of Lkb1 in cultured embryonic pancreas destabilizes tissue architecture to generate precancerous-like lesions. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A41.