生体分子研究と治療学ジャーナル

概要

Tolomeres and Cancer

Iqbal RK, Azam I and Khalid R

Telomere protects the chromosomes in normal cells, and their shortening due to cell divisions and oxidative stress induces telomere shortening causing chromosomal instability. Telomerase is an enzyme that adds TTAGG telomeric repeats at chromosomal ends. The activity of telomerase enzyme plays a significant role in initiation and progression of cancer cells. In cancer cells the telomere length is maintained by telomerase enzyme. Cancer cells survive due to the activity of telomerase enzyme due to which the length of telomere is maintained and cell evades cell death mechanisms. In cancer cells telomere shortening or dysfunctional telomeres suppress cancer progression and development due to the activation of cellular senescence pathway. In this review we summarize telomere structure, function and the role telomere plays in cancer development and progression. Hermen J. Muller and Barbara McClintock identified telomere as a structure present at the ends of the chromosomes. The word telomere is derived from the Greek word “telos” which means ends and “meres” means part. Shorter telomere length or the complete absence of telomere induces end to end fusion of the chromosomes and ultimately cause cellular senescence or cell death. James D Watson in 1970s termed end replication problem in which during DNA replication, the DNA dependant polymerase does not replicates completely at the 5’ terminal end leaving small regions of the telomere uncopied. In 1960 Leonard Hayflick and his colleagues identified that the human diploid cell can undergo limited number of cell divisions in culture. The maximum number of divisions that a cell can achieve in-vitro is known as Hayflick limit which was termed after leonard Hayflick. When the cells reaches to a limit where they can no longer divide will eventually go under biochemical and morphological changes that eventually leads to cell cycle arrest, a process known as “cellular senescence. The telomerase is an enzyme that functions to add telomere repeats to the ends of the chromosomes and was identified in 1984 by Elizbeth and her collague. The presence of telomerase enzyme activity was also identified in human cancer cell lines by Gregg in 1989. Another study conducted by Greider and associates showed the absence of telomerase enzyme in normal somatic cell. Shay and Harley in 1990s detected the presence of telomerase activity in 90 out of 101 human tumor cell samples isolated from 12 different tumor types, whereas they have found no activity in normal somatic samples (n=50) isolated from 4 different tissue types. Since then various studies on 2600 human tumor samples have shown the telomerase activity in around 90% of different tumor cells. The existence of telomerase activity in cancer cells clearly demonstrates a major role of this enzyme in cancer pathogenesis. Telomeres plays a critical role in cancer, aging, Progeria (premature aging) and various other age related disorders due to which telomere and telomerase enzyme are recently an active area of research.