Abstract 5140: The expression and function of LAP2 and its interaction with Chmp1A in pancreatic cancer

Abstract

Abstract Introduction: Chromatin modifying protein 1A (Chmp1A) suppresses pancreatic cancer growth by the activation of ATM and p53. To understand the mechanisms underlying the function of Chmp1A in pancreatic cancer, Chmp1A associated proteins were identified using proteomic analysis. Lamina-associated polypeptide 2 (LAP2) protein isoforms were found to interact with Chmp1A. LAP2 has been shown to interact with Retinoblastoma (Rb) tumor suppressor and shown to be up-regulated in most proliferating cancer cells. However, the function of LAP2 in pancreatic cancer has been poorly understood. In this study, we propose that LAP2 protein functions as tumor suppressor by interacting with Chmp1A in pancreatic cancer. Experimental procedures: LAP2 transcripts were determined by RT-PCR and LAP2 proteins by WB and microscopic analysis in pancreatic cancer cells compared to normal pancreatic cells. We then tested the function of LAP2 by examining the effect of its overexpression on cancer cell growth. We also tested the interaction between Chmp1A and LAP2 by examining LAP2 expression in Chmp1A overexpressing or silenced cells and vice versa. Results: The level of LAP2 transcripts and proteins was increased in pancreatic cancer, compared to normal cells. Interestingly, LAP2 protein level was increased in cells derived from well, but not poorly differentiated pancreatic cancers. Immunostaining demonstrated an increased and altered cellular expression of LAP2, compared to normal. LAP2 expression was increased in Chmp1A overexpressing cells but decreased in Chmp1A silenced cells. In addition, Chmp1A expression was increased in LAP2 overexpressing cells. Summary: The expression of LAP2 isoforms were increased in tumor cells, compared to normal pancreatic cells. LAP2 overexpression study suggests its functions as tumor suppressor in pancreatic cancer. Immunocytochemical analysis suggests that the increased and altered expression of LAP2 might be important for its function in pancreatic cancer. Our data also indicates that there is comparable change in the expression between Chmp1A and LAP2 in pancreatic cancer cells. Citation Format: Maiyon Park. The expression and function of LAP2 and its interaction with Chmp1A in pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5140.