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KMID : 0620920020340020159
Experimental & Molecular Medicine
2002 Volume.34 No. 2 p.159 ~ p.166
HPV E6 antisense induces apoptosis in CaSki cells via suppression of E6 splicing
Do Young Yoon/Cheong Weon Cho
Ha Ryoung Poo/Young Sik Cho/Min Chul Cho/Kyung Ae Lee/Shin Je Lee/Sue Nie Park/In Ki Kim/Yong Keun Jung/Yong Kyung Choe/Young Il Yeom/In Seong Choe/Do Young Yoon
Abstract
Cervical cancer is known to be highly associated with viral oncogene E6 and E7 of human papilloma virus. Down-regulation of oncogene expression by antisense-based gene therapy has been extensively studied. To investigate the effect of HPV 16 E6 antisense nucleic acid (AS) on cervical cancer cells, human cervical cancer cell lines, CaSki and SiHa cells harboring HPV 16 genome were transfected with plasmid containing E6(AS). The decreased viability and the apoptotic morphology were observed in E6(AS)-transfected cervical cancer cell lines. By 6 h after transfection, inhibition of E6 splicing, rapid upregulations of p53 and a p53-responsive protein, GADD45, were displayed in E6(AS)-transfected CaSki cells. Furthermore, E6(AS) induced loss of mitochondrial transmembrane potential, release of mitochondrial cytochrome c into the cytoplasm, and subsequent activation of caspase-9 and caspase-3. These results indicate that HPV 16 E6(AS) induces apoptosis in CaSki cells via upregulation of p53 and release of cytochrome c into cytoplasm, consequently activating procaspase-9 and procaspase-3.
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