Eef1a2 promotes cell growth, inhibits apoptosis and activates JAK/STAT and AKT signaling in mouse plasmacytomas.
BACKGROUND
The canonical function of EEF1A2, normally expressed only in muscle, brain, and heart, is in translational elongation, but recent studies suggest a non-canonical function as a proto-oncogene that is overexpressed in a variety of solid tumors including breast and ovary. Transcriptional profiling of a spectrum of primary mouse B cell lineage neoplasms showed that transcripts encoding EEF1A2 were uniquely overexpressed in plasmacytomas (PCT), tumors of mature plasma cells. Cases of human multiple myeloma expressed significantly higher levels of EEF1A2 transcripts than normal bone marrow plasma cells. High-level expression was also a feature of a subset of cell lines developed from mouse PCT and from the human MM.


RESULTS
Heightened expression of EEF1A2 was not associated with increased copy number or coding sequence mutations. shRNA-mediated knockdown of Eef1a2 transcripts and protein was associated with growth inhibition due to delayed G1-S progression, and effects on apoptosis that were seen only under serum-starved conditions. Transcriptional profiles and western blot analyses of knockdown cells revealed impaired JAK/STAT and PI3K/AKT signaling suggesting their contributions to EEF1A2-mediated effects on PCT induction or progression.


CONCLUSIONS
EEF1A2 may play contribute to the induction or progression of some PCT and a small percentage of MM. Eef1a2 could also prove to be a useful new marker for a subset of MM and, ultimately, a possible target for therapy.
Li
Zhaoyang
Z
Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA.
Qi
Chen-Feng
CF
Shin
Dong-Mi
DM
Zingone
Adriana
A
Newbery
Helen J
HJ
Kovalchuk
Alexander L
AL
Abbott
Catherine M
CM
Morse
Herbert C
HC
D000818:Animals; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D016895:Culture Media, Serum-Free; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D053612:Janus Kinases / Q000378:metabolism*; D051379:Mice; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000235:genetics; D009101:Multiple Myeloma / Q000235:genetics / Q000473:pathology; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism*; D010950:Plasma Cells / Q000378:metabolism; D010954:Plasmacytoma / Q000201:enzymology* / Q000473:pathology*; D000090063:Proto-Oncogene Mas; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D016895:Culture Media, Serum-Free; C503235:Eef1a2 protein, mouse; C000715470:MAS1 protein, human; D020648:Peptide Elongation Factor 1; D000090063:Proto-Oncogene Mas; D050791:STAT Transcription Factors; D053612:Janus Kinases; D051057:Proto-Oncogene Proteins c-akt