title: High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell.
abstract: Overexpression of high-mobility group box 2 (HMGB2) is recently reported in several malignant cancers and was correlated with poor response to preoperative chemoradiotherapy of colorectal cancer patients. To enhance the chemoradiotherapy efficacy, the biological function of HMGB2 was investigated with respect to radiation response. HMGB2 gene knockdown cells were constructed by infecting shRNA expressing lentivirus and clonogenic assay was performed to count the radiosensitivity. HMGB2 knockdown sensitized HCT-116 and HT-29 colorectal cancer cells to ionizing radiation. This could be due to an increased DNA damage and an inefficient DNA damage repair in HMGB2 knockdown cells. In addition, an exposure to radiation downregulated HMGB2 expression in colorectal cancer cells with an intact TP53 gene. HMGB2 gene expression of TP53-mutant cell was not affected by irradiation. p53-mediated downregulation of HMGB2 was confirmed by direct activation of p53 using Nutlin-3 or by inducing p53 expression using Tet-On system. Luciferase reporter assay showed that HMGB2 promoter activity was inversely correlated with the amount p53 cotransfected. Our study revealed that HMGB2 is necessary to protect colorectal cancer cells from DNA damage and efficient DNA repair and p53-mediated downregulation is a critical mechanism of modulating HMGB2 expression.
authors.affiliation: Department of Radiation Oncology, Sanggye Paik Hospital, Inje University, Seoul, Republic of Korea.
authors.forename: Young-Joo
authors.initials: YJ
authors.lastname: Shin
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Kim
authors.forename: Moon-Sun
authors.initials: MS
authors.lastname: Kim
authors.forename: Joonseok
authors.initials: J
authors.lastname: Lee
authors.forename: Miae
authors.initials: M
authors.lastname: Kang
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jeong
mesh_terms: D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D055785:Gene Knockdown Techniques; D045325:HCT116 Cells; D024261:HMGB2 Protein / Q000235:genetics*; D019073:HT29 Cells; D006801:Humans; D011836:Radiation Tolerance / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D024261:HMGB2 Protein; D016159:Tumor Suppressor Protein p53