The tumor cell and telomerase.
Imbalanced activity of the mechanism that controls cell division is a prerequisite for malignant transformation of a normal cell. The present review considers this multi-step mechanism, which is usually called the G1-S checkpoint. Besides, tumor cells are characterized by the presence of telomerase, an enzyme responsible for restoration of chromosome ends after replication and thus providing for unlimited cell division. The main point of the present article is to find out whether the activation of telomerase is controlled by the G1-S checkpoint or does not depend on it. The principal components of the G1-S checkpoint, such as cyclin-dependent kinases, retinoblastoma and E2F proteins, control the activity of telomerase. In their turn, they accumulate and transmit signals from various sources inside and outside the cell. Thus, various changes in tumor cells can activate telomerase through the G1-S checkpoint. Such are the suggested effects on telomerase of Myc, p53, Waf1, protein kinases B and C, Wnt5A, TGFbeta, WT1, and estrogens. However, Myc, p53, WT1, estrogens, protein kinases B and C, and TGFbeta can also directly influence telomerase independently of the G1-S checkpoint mechanism. Moreover, in 30% of human tumors the gene of the key subunit of telomerase (hTERT) is amplified, possibly due to chromosomal rearrangements unassociated with the activity of the G1-S checkpoint. Thus, telomerase seems to be activated not by a single agent but due to combined action of various factors, both with involvement of the G1-S checkpoint mechanism and independently of it.
Altshuler
M L
ML
Moscow Institute of Medical Ecology, Health Care Department of Moscow, Moscow 117638, Russia. 7034.g23@g23.relcom.ru
Severin
S E
SE
Glukhov
A I
AI
D000818:Animals; D002453:Cell Cycle; D004789:Enzyme Activation; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology*; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism
D019098:Telomerase