The functional role of MAP3K2 in pancreatic ductal adenocarcinoma

Ibrahim, Arig (2025): The functional role of MAP3K2 in pancreatic ductal adenocarcinoma. Dissertation, LMU München: Faculty of Medicine

Abstract

MAP kinases serve important functions in modulating fundamental pathways, particularly those related to cell cycle progression, proliferation, differentiation, and apoptosis. The serine/threonine kinase MAP3K2 has been identified as a potential proto-oncogene in various tumor types and is the subject of ongoing oncological research. Previous studies have also suggested a potentially oncogenic role of MAP3K2 in pancreatic ductal adenocarcinoma (PDAC), a malignant tumor typically associated with a very poor prognosis. This study aimed to investigate the functional relevance of MAP3K2 in PDAC by combining RNA interference-based gene silencing in vitro with bioinformatic analyses of publicly available datasets. Following confirmation of MAP3K2 mRNA and MAP3K2 protein expression in five PDAC cell lines, siRNA-mediated knockdown was performed in PANC-1 and MIA PaCa-2 cells. Functional assays revealed a significant increase in the S-phase cell population and enhanced viability, particularly in PANC-1 cells, while apoptosis rates remained unaffected. Bioinformatic analysis of TCGA and CPTAC datasets revealed significantly elevated MAP3K2 mRNA and MAP3K2 protein expression in PDAC tissues relative to normal pancreas, with no evidence that this overexpression was driven by somatic mutations or copy number alterations. Additionally, MAP3K2 expression was not an independent prognostic factor for patient survival. In summary, the findings suggest that, contrary to its proposed proto-oncogenic function, MAP3K2 may act in a regulatory and potentially protective manner in PDAC cells, possibly as part of an adaptive response to oncogenic signals. This suggests a complex, context-dependent role for MAP3K2 in PDAC pathophysiology.

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: PDAC, PAAD, pancreatic cancer, MAP kinases, RAS-RAF-MAP kinase pathway, MAP3K2, MEKK2
• Subjects: 600 Technology, Medicine; 600 Technology, Medicine > 610 Medical sciences and medicine
• Faculties: Faculty of Medicine
• Language: English
• Date of oral examination: 11. December 2025
• 1. Referee: Bazhin, Alexander
• Signature of the printed copy: 0700/UMD 22773