[HTML][HTML] An extra copy of p53 suppresses development of spontaneous Kras-driven but not radiation-induced cancer

EJ Moding, HD Min, KD Castle, M Ali, L Woodlief… - JCI insight, 2016 - ncbi.nlm.nih.gov
EJ Moding, HD Min, KD Castle, M Ali, L Woodlief, N Williams, Y Ma, Y Kim, CL Lee
JCI insight, 2016ncbi.nlm.nih.gov
The tumor suppressor p53 blocks tumor progression in multiple tumor types. Radiation-
induced cancer following exposure to radiation therapy or space travel may also be
regulated by p53 because p53 has been proposed to respond to DNA damage to suppress
tumorigenesis. Here, we investigate the role of p53 in lung carcinogenesis and
lymphomagenesis in LA-1 Kras G12D mice with wild-type p53 or an extra copy of p53 (super
p53) exposed to fractionated total body irradiation with low linear energy transfer (low-LET) …
Abstract
The tumor suppressor p53 blocks tumor progression in multiple tumor types. Radiation-induced cancer following exposure to radiation therapy or space travel may also be regulated by p53 because p53 has been proposed to respond to DNA damage to suppress tumorigenesis. Here, we investigate the role of p53 in lung carcinogenesis and lymphomagenesis in LA-1 Kras G12D mice with wild-type p53 or an extra copy of p53 (super p53) exposed to fractionated total body irradiation with low linear energy transfer (low-LET) X-rays or high-LET iron ions and compared tumor formation in these mice with unirradiated controls. We found that an additional copy of p53 suppressed both Kras-driven lung tumor and lymphoma development in the absence of radiation. However, an additional copy of p53 did not affect lymphoma development following low-or high-LET radiation exposure and was unable to suppress radiation-induced expansion of thymocytes with mutated Kras. Moreover, radiation exposure increased lung tumor size in super p53 but not wild-type p53 mice. These results demonstrate that although p53 suppresses the development of spontaneous tumors expressing Kras G12D, in the context of exposure to ionizing radiation, an extra copy of p53 does not protect against radiation-induced lymphoma and may promote Kras G12D mutant lung cancer.
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