Open AccessBasic mechanisms of high‐risk human papillomavirus‐induced carcinogenesis: Roles of E6 and E7 proteins
Author(s) -
NarisawaSaito Mako,
Kiyono Tohru
Publication year - 2007
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2007.00546.x
Subject(s) - carcinogenesis , retinoblastoma , cervical cancer , cancer research , ubiquitin ligase , retinoblastoma protein , biology , human papillomavirus , mechanism (biology) , transcription factor , hpv infection , cervix , medicine , gene , ubiquitin , cancer , oncology , immunology , genetics , cell cycle , philosophy , epistemology
Human papillomaviruses (HPV) are believed to be the primary causal agents for development of pre‐neoplastic and malignant lesions of the uterine cervix, and high‐risk types such as type 16 and 18 are associated with more than 90% of all cervical carcinomas. The E6 and E7 genes of HPV are thought to play causative roles, since E6 promotes the degradation of p53 through its interaction with E6AP, an E3 ubiquitin ligase, whereas E7 binds to the retinoblastoma protein (pRb) and disrupts its complex formation with E2F transcription factors. Although prophylactic vaccines have become available, it is still necessary to clarify the mechanisms of HPV‐induced carcinogenesis because of the widespread nature of HPV infection. Approximately 493 000 new cases of cervical cancer are diagnosed each year with approximately 274 000 mortalities due to invasive cervical cancer. In the present article, the mechanisms of HPV16 E6‐ and E7‐induced multistep carcinogenesis and recently identified functions of these onco‐proteins are reviewed. ( Cancer Sci 2007; 98: 1505–1511)