Overexpression of the MEN/ELL protein, an RNA polymerase II elongation factor, results in transformation of Rat1 cells with dependence on the lysine-rich region

The MEN gene (also called ELL) encodes an RNA polymerase II elongation factor that has been implicated in t(11;19)(q23;p13.1) translocation in myeloid leukemias. The function of another elongation factor, elongin, is known to be inhibited by VHL tumor suppressor protein in vitro, suggesting the possible relationship of aberrant transcriptional elongation to oncogenesis. We overexpressed the MEN protein in Rat1 fibroblasts to evaluate its transforming activity, MEN-overexpressing cells acquired the capacity for anchorage-independent growth, In addition, the growth factor requirement was decreased in these cells, However, cells expressing a deletion mutant of MEN lacking the lysine-rich region did not exhibit such biological abilities, c-Fos protein expression and AP-1 activity were elevated in the MEN-expressing cells, which might be part of the mechanism responsible for the transformation, The c-fos mRNA, the expression of which is known to be regulated partly at the stage of transcriptional elongation, appeared earlier in the MEN-expressing cells than in cells transfected with an empty vector or the deletion mutant lacking the lysine-rich region after stimulation with epidermal growth factor, The RNA polymerase II elongation factor MEN may play an important role in the regulation of cell proliferation.