A subtle change in p38 MAPK activity is sufficient to suppress in vivo tumorigenesis.
Emerging evidence supports a role for p38 MAPK in negative regulation of tumorigenesis. Here we show that a subtle activation of p38 MAPK is sufficient to suppress tumorigenesis as measured by the ability to form tumors when MKK6-inducible cells were explanted into nude mice. On the other hand, this activation of p38 MAPK did not necessarily cause an immediate inhibition of cell growth in vitro as measured by standard MTS assay. This data uncovers a new methodology for anti-cancer drugs screening and suggests that a substantial number of potential anti-tumor compounds, such as activators of MKK6/p38 signaling, was missed out in previous high throughput screens based on conventional growth inhibition assays.
Timofeev
Oleg
O
Cell Cycle Control and Tumorigenesis Group, Institute of Molecular and Cell Biology, Singapore.
Lee
Ting Yi
TY
Bulavin
Dmitry V
DV
D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D016922:Cellular Senescence; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D048669:MAP Kinase Kinase 6 / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology / Q000503:physiopathology*; D014183:Transplantation, Heterologous; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D048051:p38 Mitogen-Activated Protein Kinases; D048669:MAP Kinase Kinase 6; C482567:Map2k6 protein, mouse