Atypical expression of ErbB3 in myeloma cells: cross-talk between ErbB3 and the interferon-alpha signaling complex.
We have previously demonstrated that the responsiveness of multiple myeloma (MM) cells to interferon-alpha (IFN-alpha) stimulation is variable, with an atypical growth response displayed by some cells. Here we report the ability of IFN-alpha to induce tyrosine phosphorylation of a 180 kDa band in the KAS-6/1 MM cell line, which is growth responsive to IFN-alpha. 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-alpha 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-alpha transactivated ErbB3 in the DP-6 transfectants, it did not confer growth responsiveness to IFN-alpha. Interestingly, silencing ErbB3 expression in the KAS-6/1 cells decreased the overall growth response to IFN-alpha and to interleukin-6. These results suggest that ErbB3 expression alone does not uniquely confer IFN-alpha growth responsiveness, but instead may amplify proliferation rates in MM cells that have acquired atypical expression of this receptor.
Walters
Denise K
DK
Department of Immunology, Tumor Biology Program, Mayo Graduate and Medical Schools, Mayo Clinic/Foundation, Rochester, MN 55905, USA.
French
Jena D
JD
Arendt
Bonnie K
BK
Jelinek
Diane F
DF
D002455:Cell Division / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D046911:Macromolecular Substances; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism; D009101:Multiple Myeloma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D034741:RNA, Small Interfering / Q000494:pharmacology; D020239:Receptor Cross-Talk / Q000502:physiology*; D020893:Receptor, ErbB-3 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000378:metabolism; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D004268:DNA-Binding Proteins; D016898:Interferon-alpha; D046911:Macromolecular Substances; D034741:RNA, Small Interfering; D017471:Receptors, Interferon; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D014443:Tyrosine; D020893:Receptor, ErbB-3; D020928:Mitogen-Activated Protein Kinases