Molecular biology of cervical cancer and its precursors.
Cervical cancer develops from well-defined precursor lesions referred to as either cervical intraepithelial neoplasia or squamous intraepithelial lesions. It is now known that specific types of human papillomaviruses (HPV) are the principal etiologic agents for both cervical cancer and its precursors. The high-oncogenic-risk HPV types associated with invasive cervical cancer produce two oncoproteins, designated E6 and E7, which interact with endogenous cell cycle regulatory proteins, including p53 and Rb. The interaction of virally derived and endogenous cellular proteins converges in deregulation of cell cycle progression and appears to be critical for the development of cervical cancers. However, the development of cervical cancer is a multistep process that cannot be explained simply by infection with specific types of HPV. One additional event that appears to play a role in tumor progression is integration of HPV DNA into the host genome. Integration of HPV DNA frequently disrupts the E2 open reading frames, resulting in overexpression of the E6 and E7 oncoproteins and possibly causing genomic instability. Additional cofactors and mutational events may be important in the pathogenesis of invasive cervical cancers and may include chromosomal rearrangements, loss of constitutional heterozygosity, and proto-oncogene activation.
Park
T W
TW
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Fujiwara
H
H
Wright
T C
TC
D002472:Cell Transformation, Viral; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D014412:Tumor Virus Infections / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000209:etiology / Q000235:genetics*
C000715470:MAS1 protein, human; D009856:Oncogene Proteins, Viral; D000090063:Proto-Oncogene Mas; C062495:oncogene protein E7, Human papillomavirus type 6