ALTERED EXPRESSION OF ANNEXIN-II IN HUMAN B-CELL LYMPHOMA CELL-LINES

Annexin II is a growth-regulated gene, whose expression is significant ly increased in various human cancers. We examined annexin II expressi on in 11 human B-cell lymphoma cell lines and in normal B-cells. Wide variation was observed in the levels of annexin II in these cell lines . Annexin II overexpression was observed in 5 cell lines, while signif icantly reduced expression was observed in Raji, OMA-BL-I and REH cell lines. Analysis of the annexin II gene, mRNA and protein in Raji and OMA-BL-I cell lines indicated that annexin II gene was unaltered and t hat a low level of annexin II transcripts are produced in these cells. Down-regulation of annexin II expression was at the transcriptional l evel, and no reexpression of annexin II was observed after treatment o f cells with demethylating agents. Thus methylation of the annexin II gene does not appear to be responsible for annexin II down-regulation. A slow migrating altered form of annexin II was detected in Raji and OMA-BL-I cells, which was detected with the anti-chicken annexin II an tiserum, but not with the anti-human annexin II antiserum. The slow mi grating annexin II species was found to be sensitive to dephosphorylat ion by calf intestinal alkaline phosphatase, resulting in reduction of the size of the protein on SDS-polyacrylamide gels. The phosphorylate d annexin II was also observed in nuclear extracts of human K562 and H eLa cells. Thus, Raji and OMA-BL-I cells exclusively produce a phospho rylated form of annexin II, and phosphorylated annexin LI may be impor tant for cell survival and proliferation.