Abstract
We have previously demonstrated that the responsiveness of multiple myeloma (MM) cells to interferon-alpha (IFN-α) stimulation is variable, with an atypical growth response displayed by some cells. Here we report the ability of IFN-α to induce tyrosine phosphorylation of a 180 kDa band in the KAS-6/1 MM cell line, which is growth responsive to IFN-α. Further characterization demonstrated that this band corresponds to ErbB3. To our knowledge, this is the first report of ErbB3 expression in a cell type of the hematopoietic lineage. Although ErbB receptors have been shown to crosscommunicate with various other receptors, our results show for the first time that the IFN-α receptor can crosscommunicate with ErbB3. To address the significance of these observations, we transfected ErbB3-negative DP-6 MM cells with ErbB3 and used siRNA to silence ErbB3 in the KAS-6/1 cell line. Although IFN-α transactivated ErbB3 in the DP-6 transfectants, it did not confer growth responsiveness to IFN-α. Interestingly, silencing ErbB3 expression in the KAS-6/1 cells decreased the overall growth response to IFN-α and to interleukin-6. These results suggest that ErbB3 expression alone does not uniquely confer IFN-α growth responsiveness, but instead may amplify proliferation rates in MM cells that have acquired atypical expression of this receptor.
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Acknowledgements
We thank Drs Nita Maihle and Hakjoo Lee for helpful discussions and Dr Anne J Novak for reading the manuscript. We also acknowledge the technical expertise of Renee C Tschumper. This work was supported by National Institutes of Health NCI Grants CA62242 and CA62228 (DFJ).
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Walters, D., French, J., Arendt, B. et al. Atypical expression of ErbB3 in myeloma cells: cross-talk between ErbB3 and the interferon-α signaling complex. Oncogene 22, 3598–3607 (2003). https://doi.org/10.1038/sj.onc.1206512
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DOI: https://doi.org/10.1038/sj.onc.1206512
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