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21984975
PTEN is a major tumor suppressor in pancreatic ductal adenocarcinoma and regulates an NF-κB-cytokine network.

Cancer Discov, 2011/7;1(2):158-69.

Ying H[1], Elpek KG, Vinjamoori A, Zimmerman SM, Chu GC, Yan H, Fletcher-Sananikone E, Zhang H, Liu Y, Wang W, Ren X, Zheng H, Kimmelman AC, Paik JH, Lim C, Perry SR, Jiang S, Malinn B, Protopopov A, Colla S, Xiao Y, Hezel AF, Bardeesy N, Turley SJ, Wang YA, Chin L, Thayer SP, DePinho RA

Affiliations

PMID: 21984975DOI: 10.1158/2159-8290.CD-11-0031

Impact factor: 38.272

Abstract
Initiation of pancreatic ductal adenocarcinoma (PDAC) is driven by oncogenic KRAS mutation, and disease progression is associated with frequent loss of tumor suppressors. In this study, human PDAC genome analyses revealed frequent deletion of the PTEN gene as well as loss of expression in primary tumor specimens. A potential role for PTEN as a haploinsufficient tumor suppressor is further supported by mouse genetic studies. The mouse PDAC driven by oncogenic Kras mutation and Pten deficiency also sustains spontaneous extinction of Ink4a expression and shows prometastatic capacity. Unbiased transcriptomic analyses established that combined oncogenic Kras and Pten loss promotes marked NF-κB activation and its cytokine network, with accompanying robust stromal activation and immune cell infiltration with known tumor-promoting properties. Thus, PTEN/phosphoinositide 3-kinase (PI3K) pathway alteration is a common event in PDAC development and functions in part to strongly activate the NF-κB network, which may serve to shape the PDAC tumor microenvironment.
MeSH terms
Adenocarcinoma; Animals; Animals, Genetically Modified; Carcinoma, Pancreatic Ductal; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p16; Cytokines; Genes, Tumor Suppressor; Humans; Mice; Mice, Inbred C57BL; Mutation; NF-kappa B; PTEN Phosphohydrolase; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins p21(ras)
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