In vivo and in vitro studies suggest a possible involvement of HPV infection in the early stage of breast carcinogenesis via APOBEC3B induction.

In vivo and in vitro studies suggest a possible involvement of HPV infection in the early stage of breast carcinogenesis via APOBEC3B induction.
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DOI:
10.1371/journal.pone.0097787
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Yamamoto N
Yamamoto N
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ohba K;Ichiyama K;Yajima M;Gemma N;Nikaido M;Wu Q;Chong P;Mori S;Yamamoto R;Wong JE;Yamamoto N

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使用新的DNA芯片技术,新加坡乳腺癌(BC)患者感染高危人乳头瘤病毒(HPV)的比例从25%到100%不等(平均为31%)。早期BC组HPV阳性率较高,雌激素受体(ER)阳性组HPV感染率显著高于BC组。这种独特的HPV与体内BC的相关性促使我们调查HPV在乳腺癌发生的早期阶段的可能参与。利用稳定转染HPV-18的正常乳腺上皮细胞,我们发现胞苷脱氨酶APOBEC3B(A3B)的mRNA明显上调,据报道,A3B是BC突变的来源。HPV18E6、E7和A3B基因的shRNA可使HPV18E6、E7和A3B细胞发生γ断裂。这些结果有力地表明,HPV通过A3B诱导在BC的早期癌变过程中起积极作用。
High prevalence of infection with high-risk human papilloma virus (HPV) ranging from 25 to 100% (average 31%) was observed in breast cancer (BC) patients in Singapore using novel DNA chip technology. Early stage of BC demonstrated higher HPV positivity, and BC positive for estrogen receptor (ER) showed significantly higher HPV infection rate. This unique association of HPV with BC in vivo prompted us to investigate a possible involvement of HPV in early stages of breast carcinogenesis. Using normal breast epithelial cells stably transfected with HPV-18, we showed apparent upregulation of mRNA for the cytidine deaminase, APOBEC3B (A3B) which is reported to be a source of mutations in BC. HPV-induced A3B overexpression caused significant γH2AX focus formation, and DNA breaks which were cancelled by shRNA to HPV18 E6, E7 and A3B. These results strongly suggest an active involvement of HPV in the early stage of BC carcinogenesis via A3B induction.
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