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

Alba Granados-Jaén1, Maria Angulo-Ibáñez1, Xavier Rovira-Clavé1

  • 1Celltec-UB, Department of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, Barcelona, Spain.

Oncotarget
|October 30, 2016
PubMed

Insights

The absence of MAPK7 delays tumor development in mice lacking ATM, a key DNA damage response protein. This suggests MAPK7 inhibition could partially restore DNA repair and apoptosis, hindering thymic lymphoma growth.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cellular Signaling

Background:

  • Ataxia-telangiectasia mutated (ATM) is a crucial kinase regulating cell cycle arrest and DNA repair following DNA damage.
  • Loss-of-function mutations in ATM are linked to increased tumorigenesis.
  • Mitogen-activated protein kinase 7 (MAPK7) is implicated in cancer, often promoting cell survival and growth, but its interaction with tumor suppressors like ATM is unclear.

Purpose of the Study:

  • To investigate the functional relationship between ATM and MAPK7 in the context of DNA damage response and tumorigenesis.
  • To determine if MAPK7 influences tumor development in mice deficient in ATM.
  • To elucidate the impact of MAPK7 absence on thymocyte response to DNA damage and ionizing radiation.

Main Methods:

  • Utilized Atm-/- mice to study spontaneous tumor development.
  • Compared DNA damage response in Atm-/- and Mapk7-/-Atm-/- thymocytes.
  • Assessed DNA damage markers (e.g., phosphorylation of H2AX) and apoptotic responses after ionizing radiation exposure.

Main Results:

  • Absence of MAPK7 significantly delayed death from spontaneous tumors in Atm-/- mice.
  • Mapk7-/-Atm-/- thymocytes showed enhanced DNA damage response, indicated by increased H2AX phosphorylation.
  • These thymocytes also exhibited a restored apoptotic response to ionizing radiation compared to Atm-/- controls.

Conclusions:

  • ATM and MAPK7 play antagonistic roles in the DNA damage response within thymocytes.
  • Lack of MAPK7 can partially restore the DNA damage response in Atm-deficient thymocytes.
  • Inhibiting MAPK7 may represent a therapeutic strategy to impede thymic lymphoma growth in ATM-deficient cancers.
Keywords:
BMK1DNA damage responsethymic lymphomathymocyteγH2AX

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