지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2016.1
- 수록면
- 1,130 - 1,140 (11page)
이용수
초록· 키워드
오류제보하기
Purpose Histone deacetylase (HDAC) inhibitors radiosensitize tumor cells. To elucidate mechanisms underlying radiosensitization by HDAC inhibition, understanding of differential contributions of HDAC isotypes is needed. The aim of this study was to investigate involvement of known HDAC isotypes in modulation of cellular radiosensitivity.
Materials and Methods Because pharmacologic HDAC inhibitors lack isotype-specificity, RNA interference against 11 HDAC isotypes was used to inhibit HDAC in an isotype-specific manner. Radiation cell survival was evaluated using a clonogenic assay in SQ20B cells transfected with small interfering RNA specifically targeting HDAC isotypes. Immunocytochemistry was performed for detection of !H2AX foci. Protein expression was measured using Western blotting.
Results Among 11 HDAC isotypes tested, specific inhibition of 7 isotypes (HDAC1, HDAC3, HDAC4, HDAC6, HDAC7, HDAC10, and HDAC11) enhanced radiation lethality in SQ20B cells.
Radiosensitization by inhibition of these HDAC isotypes was accompanied by delay of DNA double strand break repair. Radiosensitivity of SQ20B cells was not altered by selective inhibition of the remaining four isotypes (HDAC2, HDAC5, HDAC8, and HDAC9). Inhibition of HDAC isotypes resulted in downregulation of various proteins involved in pro-survival and DNA damage repair pathways.
Conclusion Isotype-specificity exists in HDAC inhibition-induced radiosensitization. Different HDAC isotypes are differentially involved in modulation of cellular radiosensitivity.
목차
등록된 정보가 없습니다.
참고문헌 (24)
참고문헌 신청
Witt O / 2009 / HDAC family : what are the cancer relevant targets? / Cancer Lett 277:8~21
Lopez CA / 2007 / Phenylbutyrate sensitizes human glioblastoma cells lacking wild-type p53 function to ionizing radiation / Int J Radiat Oncol Biol Phys 69:214~220
Banuelos CA / 2007 / Radiosensitization by the histone deacetylase inhibitor PCI-24781 / Clin Cancer Res 13(22 Pt 1):6816~6826
Geng L / 2006 / Histone deacetylase(HDAC)inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer / Cancer Res 66:11298~11304
Munshi A / 2006 / Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci / Mol Cancer Ther 5:1967~1974
Lopez CA / 2007 / Phenylbutyrate sensitizes human glioblastoma cells lacking wild-type p53 function to ionizing radiation / Int J Radiat Oncol Biol Phys 69:214~220
Banuelos CA / 2007 / Radiosensitization by the histone deacetylase inhibitor PCI-24781 / Clin Cancer Res 13(22 Pt 1):6816~6826
Geng L / 2006 / Histone deacetylase(HDAC)inhibitor LBH589 increases duration of gamma-H2AX foci and confines HDAC4 to the cytoplasm in irradiated non-small cell lung cancer / Cancer Res 66:11298~11304
Munshi A / 2006 / Vorinostat, a histone deacetylase inhibitor, enhances the response of human tumor cells to ionizing radiation through prolongation of gamma-H2AX foci / Mol Cancer Ther 5:1967~1974
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