High-mobility group box 2 (HMGB2) modulates radioresponse and is downregulated by p53 in colorectal cancer cell

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 wi...

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Bibliographic Details
Published in:Cancer biology & therapy 2013-03, Vol.14 (3), p.213-221
Main Authors: Shin, Young-Joo, Kim, Mi-Sook, Kim, Moon-Sun, Lee, Joonseok, Kang, Miae, Jeong, Jae-Hoon
Format: Article
Language:English
Subjects:
Cell Line, Tumor
colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - metabolism
DNA Damage
DNA Repair
Gene Expression Regulation, Neoplastic - radiation effects
Gene Knockdown Techniques
HCT116 Cells
HMGB2
HMGB2 Protein - genetics
HT29 Cells
Humans
radiation
Radiation Tolerance - genetics
Research Paper
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:1538-4047
1555-8576
DOI:10.4161/cbt.23292