Immortalization of human oral keratinocytes is associated with elevation of telomerase activity and shortening of telomere length.
Telomerase is a ribonucleoprotein complex that synthesizes TTAGGG repeat sequences at the ends of mammalian chromosomes. Its activity is found in most cancer cells and few rare normal somatic cells. To investigate whether telomerase activity and telomere length of normal human oral keratinocytes (NHOK) are altered by <high risk> human papillomaviruses (HPV), we transfected primary NHOK with type 16 HPV (HPV-16) genome and determined the activity of telomerase. HPV transfection extended the life span of NHOK and eventually induced immortalization of cells. Moderate telomerase activity was consistently observed in rapidly proliferating NHOK, and activity was not changed in HPV-16 transfected cells with extended life span. However, the activity was sharply increased when cells passed the crisis stage. Telomere length, which remained constant at approximately 6.8 kb during serial passages of NHOK, progressively shortened in HPV DNA transfected cells during the period of extended life span and continued until crisis, after which it stabilized at approximately 5 kb. These results demonstrate that immortalization of NHOK with HPV-16 DNA is associated with the activation of telomerase.
Guo
W
W
Dental Research Institute, School of Dentistry, University of California, Los Angeles, CA 90095-1668, USA.
Kang
M K
MK
Kim
H J
HJ
Park
N H
NH
D002455:Cell Division / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000502:physiology; D002472:Cell Transformation, Viral; D016679:Genome, Viral; D006801:Humans; D015603:Keratinocytes / Q000201:enzymology / Q000648:ultrastructure / Q000821:virology*; D009061:Mouth Mucosa / Q000473:pathology*; D027383:Papillomaviridae / Q000235:genetics*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000648:ultrastructure*; D014162:Transfection
D019098:Telomerase