Cellular and molecular biological aspects of cervical intraepithelial neoplasia.
Cervical cancer is one of the most common cancers in women. The development of this disease involves reversible changes in the cervical tissue leading to various cellular abnormalities and ultimately to cervical cancer. Several well-defined stages of cervical neoplasia are described, namely, precancer lesions and cancer. Squamous cell carcinomas and adenocarcinomas are most frequent among them, the former being much more common. Each stage is characterized by specific morphological changes. These changes were analyzed in the context of recent molecular biology data. Cervical carcinogenesis associated with infection with high-risk human papillomaviruses (HPVs) contains several early genes that are necessary for viral replication and among them two genes (E6 and E7) play a key role in the induction of cervical carcinogenesis. The main targets of their products are tumor-suppressor genes p53 and retinoblastoma, and their function is inhibited by E6 and E7 proteins. Both E6 and E7 are multifunctional and participate in many cellular functions associated with cell proliferation. The viral genome persists in transformed cells in episomal or integrated form (or both), and possible role of such type of persistence in tumor progression is discussed. Progression of the disease also involves many epigenetic changes. These include methylation of the genes relevant to cell proliferation and differentiation, activation of telomerase, and global changes in cellular gene expression. The cervical cancer is the first cancer that can be effectively prevented by vaccination.
Kisseljov
Fjodor
F
N. N. Blochin Cancer Research Center, Kashirskoe shoesse, Moscow, Russia.
Sakharova
Olga
O
Kondratjeva
Tatjana
T
D005260:Female; D006801:Humans; D030361:Papillomavirus Infections / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000503:physiopathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000473:pathology / Q000503:physiopathology / Q000821:virology