Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses

S. B. Kim, R. G. Bozeman, A. Kaisani, W. Kim, L. Zhang, J. A. Richardson, W. E. Wright, J. W. Shay

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Proton radiotherapy is becoming more common as protons induce more precise DNA damage at the tumor site with reduced side effects to adjacent normal tissues. However, the long-term biological effects of proton irradiation in cancer initiation compared with conventional photon irradiation are poorly characterized. In this study, using a human familial adenomatous polyposis syndrome susceptible mouse model, we show that whole-body irradiation with protons are more effective in inducing senescence-associated inflammatory responses (SIRs), which are involved in colon cancer initiation and progression. After proton irradiation, a subset of SIR genes (Troy, Sox17, Opg, Faim2, Lpo, Tlr2 and Ptges) and a gene known to be involved in invasiveness (Plat), along with the senescence-associated gene (P19Arf), are markedly increased. Following these changes, loss of Casein kinase Iα and induction of chronic DNA damage and TP53 mutations are increased compared with X-ray irradiation. Proton irradiation also increases the number of colonic polyps, carcinomas and invasive adenocarcinomas. Pretreatment with the non-steroidal anti-inflammatory drug, 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide (CDDO-EA), reduces proton irradiation-associated SIR and tumorigenesis. Thus exposure to proton irradiation elicits significant changes in colorectal cancer initiation and progression that can be mitigated using CDDO-EA.

Original languageEnglish (US)
Pages (from-to)3365-3375
Number of pages11
JournalOncogene
Volume35
Issue number26
DOIs
StatePublished - Jun 30 2016

Fingerprint

Protons
Colorectal Neoplasms
Radiation
Adenomatous Polyposis Coli
DNA Damage
Casein Kinase I
Colonic Polyps
Genes
Whole-Body Irradiation
Photons
Colonic Neoplasms
Neoplasms
Carcinogenesis
Adenocarcinoma
Anti-Inflammatory Agents
Radiotherapy
X-Rays
Carcinoma
Mutation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Radiation promotes colorectal cancer initiation and progression by inducing senescence-associated inflammatory responses. / Kim, S. B.; Bozeman, R. G.; Kaisani, A.; Kim, W.; Zhang, L.; Richardson, J. A.; Wright, W. E.; Shay, J. W.

In: Oncogene, Vol. 35, No. 26, 30.06.2016, p. 3365-3375.

Research output: Contribution to journalArticle

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