Absence of ERK5/MAPK7 delays tumorigenesis in Atm(-/-) mice

作者：Granados Jaen Alba; Angulo Ibanez Maria; Rovira Clave Xavier; Vasquez Gamez Celina Paola; Soriano Francesc X; Reina Manuel; Espel Enric

来源：Oncotarget, 2016, 7(46): 74435-74447.

DOI：10.18632/oncotarget.12908

• thymic lymphoma
• DNA damage response
• gamma H2AX
• BMK1
• thymocyte

Ataxia-telangiectasia mutated (ATM) is a cell cycle checkpoint kinase that upon activation by DNA damage leads to cell cycle arrest and DNA repair or apoptosis. The absence of Atm or the occurrence of loss-of-function mutations in Atm predisposes to tumorigenesis. MAPK7 has been implicated in numerous types of cancer with pro-survival and pro-growth roles in tumor cells, but its functional relation with tumor suppressors is not clear. In this study, we show that absence of MAPK7 delays death due to spontaneous tumor development in Atm(-/-) mice. Compared with Atm(-/-) thymocytes, Mapk7(-/-) Atm(-/-) thymocytes exhibited an improved response to DNA damage (increased phosphorylation of H2AX) and a restored apoptotic response after treatment of mice with ionizing radiation. These findings define an antagonistic function of ATM and MAPK7 in the thymocyte response to DNA damage, and suggest that the lack of MAPK7 inhibits thymic lymphoma growth in Atm(-/-) mice by partially restoring the DNA damage response in thymocytes.

• 出版日期2016-11-15