Abstract 3852: Bcl-xL and IL-6 act independently and synergistically to accelerate plasmacytopoiesis and plasma cell tumor formation in Balb/c mice.

Abstract

Abstract Accelerated development of spontaneous plasma cell tumors (PCT) occurs in mucosal-associated lymphoid tissues of mice bearing both IL-6 and BCL-XL transgenes (double transgenic (dTg)). 91% of dTG mice developed PCTs at a mean age of 89 days. In contrast, 53% of the IL-6 Tg mice developed PCTs at a mean age of 301 days and 12% BCL-XL Tg mice developed PCTs with a mean age of 433 days. The PCTs formed primarily in Peyer's Patches, medullary cords of the mesenteric lymph node and/or the lamina propria of small intestinal villi where they were preceded by massive plasma cell hyperplasia. To investigate the molecular basis of the cooperation between IL-6 and BCL-xL transgenes to accelerate PCT development we performed detailed analysis of cell lines developed from dTG mice and and spontaneous or pristane-induced tumors of Bcl-xL TG mice. All the tumors carry Ig/Myc-deregulating chromosomal translocations, which are thought to be the initiating event of PCT development. Therefore we focused on finding possible differences in secondary alterations. Although the subsets were poorly distinguished by microarray-based gene expression profiling, there were significant differences in the expression of p21, p19ARF, p53, HUWE1 and pRb as determined by western blotting and qPCR. DTG tumors were characterized by alterations in pathways governing expression of pRb that included increased expression of INK4A and down regulation of pRb itself as well as down regulation of p19ARF. Most notably we discovered discordance between protein and mRNA levels for pRb and p19Arf. Efforts to understand the molecular basis for these distinctions and their contributions to the biology of these PCT subsets are in progress. Citation Format: Tomomi Sakai, Alexander L. Kovalchuk, Herbert Morse. Bcl-xL and IL-6 act independently and synergistically to accelerate plasmacytopoiesis and plasma cell tumor formation in Balb/c mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3852. doi:10.1158/1538-7445.AM2013-3852