Mediator complex subunit 29 (MED29) is part of a large multiprotein coactivator complex that mediates regulatory signals from gene-specific activators to general transcription machinery in
RNA polymerase II mediated transcription. We previously found that MED29 is amplified and overexpressed in
pancreatic cancer and that MED29 silencing leads to decreased cell survival in PANC-1
pancreatic cancer cells with high MED29 expression. Here we further demonstrate decreased migration, invasion and colony formation in PANC-1 cells after MED29 silencing. Unexpectedly, lentiviral-based overexpression of MED29 led to decreased proliferation of NIH/3T3 cells as well as MIAPaCa-2
pancreatic cancer cells with low endogenous expression. More importantly, subcutaneous inoculation of the MED29-transduced
pancreatic cancer cells into immuno-compromised mice resulted in dramatic
tumor suppression. The mock-control mice developed large
tumors, whereas the animals with MED29-xenografts showed both decreased
tumor incidence and a major reduction in
tumor size. Gene expression analysis in the MED29-transduced
pancreatic cancer cells revealed differential expression of genes involved in control of cell cycle and cell division. The observed gene expression changes are expected to modulate the cell cycle in a way that leads to reduced cell growth, explaining the in vivo
tumor suppressive phenotype. Taken together, these data implicate MED29 as an important regulator of key cellular functions in
pancreatic cancer with both oncogenic and
tumor suppressive characteristics. Such a dualistic role appears to be more common than previously thought and is likely to depend on the genetic background of the
cancer cells and their surrounding environment.