BCL-XL and IL-6 act independently and synergistically to accelerate plasmacytopoiesis and plasma cell tumor formation in BALB/cAn mice

Wednesday, November 06, 2013 — Poster Session I
4:00 p.m. – 6:00 p.m.	FAES Academic Center (Upper-Level Terrace)	NIAID	CANCER-14

Authors

T. Sakai
A.L. Kovalchuk
W. Dubois
CF. Qi
Z. Naghashfar
D-M. Shin
H.C. Morse III
M. Potter

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)). DTG mice developed PCTs more rapidly and with a higher incidence than single Tg mice. To investigate the molecular basis for cooperation between IL-6 and BCL-XL TG in accelerating PCT development, we performed detailed analysis of cell lines developed from dTG and Bcl- XL TG mice, either spontaneous or pristane-induced. All tumors had 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. 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.