e shown that Fascin har bours ��B consensus sites in its promoter, and we have shown that Fascin e pression can be induced by NF ��B. Contribution of NF ��B to e pression of Fascin was also confirmed in a breast cancer cell line showing binding Drug_discovery of p65 to the Fascin promotor. Collectively, these findings suggest that LMP1 regulates Fascin e pression via canonical NF ��B signaling not only in lymphocytes, but potentially also in other cell types. We have previously shown that Fascin e pression can be induced by the viral oncoprotein Ta of the tumor virus Human T lymphotropic virus type 1, which belongs to the family of delta retroviridae. Beyond that, we found a novel mode of transcriptional regulation of Fascin showing the importance of NF ��B signaling in Ta mediated Fascin induction.
There fore, the LMP1 mediated induction of Fascin via NF ��B signaling may be a common mechanism of lymph otropic tumor viruses revealing a new quality of virus induced oncogenesis. All tumor viruses with naturally occurring distinct oncogenes reprogram persistently infected cells in the direction of growth promotion and survival func tions, and it is plausible that these are side effects of viral growth and propagation. Now, we have shown that not only the leukemia inducing retrovirus HTLV 1, but also the oncogenic herpesvirus EBV can induce Fascin. However, future studies are needed to address whether other viral oncoproteins like the KSHV encoded oncoprotein vFLIP, which activates both canonical and non canonical NF ��B pathways, are able to induce Fascin.
In contrast to LCLs, PEL cells do not e press Fascin, suggesting that regulation of Fascin does not only depend on cell type and on the NF ��B signaling pathway, but also on other properties of different viral oncoproteins. Conclusions Here we report for the first time that LMP1 induces Fascin in lymphocytes and this depends on canonical NF ��B sig naling. Fascin mediates invasiveness of carcinoma cells, a typical function of tumor progression. Our data indicate a contribution of Fascin to invasive migration of LMP1 e pressing lymphocytes. Collectively, our findings suggest that Fascin plays a role in viral oncogenesis. Methods Cell culture Cell lines used in this report include the Epstein Barr virus positive human lymphoblastoid B cell lines LCL B and LCL 721, the EBV LCLs LCL 3 and LCL 4, which are derived from in vitro transformation of human B lymphocytes with a recombinant ma i EBV in which the wildtype LMP1 gene had been replaced by HA LMP1, the LCL clone B2264 19 3 e pressing chimeric nerve growth factor receptor LMP1 allowing inducible LMP1 signal ing, the EBV negative Hodgkin lymphoma derived cell lines KM H2, L428, and HDLM 2, the EBV, Burkitt Lymphoma de rived B cell line Raji, the EBV?, BL derived B cell line Bjab, and the EBV? B cell line Akata, the EBV?, Kaposis sarcoma associated herpesvirus positive B cell lines Bcbl 1 and BC 3 derived from primary ef fusion lymphoma, the EBV KSHV PEL derived B cell line