PLoS ONE (Jan 2014)

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

  • Kenji Ohba,
  • Koji Ichiyama,
  • Misako Yajima,
  • Nobuhiro Gemma,
  • Masaru Nikaido,
  • Qingqing Wu,
  • PeiPei Chong,
  • Seiichiro Mori,
  • Rain Yamamoto,
  • John Eu Li Wong,
  • Naoki Yamamoto

DOI
https://doi.org/10.1371/journal.pone.0097787
Journal volume & issue
Vol. 9, no. 5
p. e97787

Abstract

Read online

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.