Speakers
Dr
Jae-Hoon Jeong
(Korea Institute of Radiological and Medical Sciences)Dr
Young-Joo Shin
(Inje University Sanggye Paik Hospital)
Description
Objectives: To improve the chemoradiotherapy efficacy in cancer patients by investigating the biological function of HMGB2 with respect to radiation response regulation.
Methods: HMGB2 gene knockdown cells were constructed by infecting shRNA expressing lentivirus. mRNA expression was measured by realtime qRT-PCR and protein level or phosphorylation was by Western blot analysis. Clonogenic assay was performed to count the radiosensitivity. Immunofluorescence staining of gamma-H2AX was examined under confocal microscope.
Results: HMGB2 knockdown sensitized HCT-116 and HT-29 colorectal cancer cells to radiation. This may be due to increase of DNA damage and delayed DNA damage repair in HMGB2 knockdown cells. Interestingly, HMGB2 expression was downregulated by ionizing radiation in colorectal cancer cells with functional TP53 gene and it was confirmed that p53 activation inhibited HMGB2 transcription.
Conclusions: Because HMGB2 was necessary to protect colorectal cancer cells from ionizing radiation, radiotherapy outcome could be enhanced by targeting HMGB2. p53-mediated downregulation of HMGB2 is an important mechanism in modulation of HMGB2 expression and may be applied to predict therapeutic efficacy.
Primary author
Dr
Jae-Hoon Jeong
(Korea Institute of Radiological and Medical Sciences)
Co-authors
Dr
Mi-Sook Kim
(Korea Institute of Radiological and Medical Sciences)
Dr
Young-Joo Shin
(Inje University Sanggye Paik Hospital)
