STAT3 regulates the growth and immunoglobulin production of BCL1 B cell lymphoma through control of cell cycle progression

STAT3 is constitutively phosphorylated on tyrosine(705) in self-renewing, C D5(+) murine B-1 lymphocytes, Nuclear extracts from untreated primary B-l o r CD5(+) BCL1 B lymphoma cells were found to contain immunoreactive STAT3 p rotein that binds to a sis-inducible element present in the promoter of the p21(waf1/cip1) tumor suppressor gene and is constitutively phosphorylated on serine(727). To determine the functional significance of constitutive ST AT3 activation in B lymphoma cells, a specific STAT3 antisense oligonucleot ide was developed and used to examine basal BCL1 cell growth and IgM produc tion. Abrogating STAT3 expression in BCL1 cells inhibited their proliferati ve capacity and induced a corresponding decrease in secretion of IgM, Cell cycle analysis showed a block in progression through G1 in BCL1 cells treat ed with the STAT3 antisense oligonucleotide, These results indicate that ST ATE controls cell growth and immunoglobulin secretion by enhancing progress ion through the G1 phase of the cell cycle in BCL1 B cell lymphoma, (C) 200 0 Academic Press.