Hallmarks, Becoming immortal

Professor Robert Weinberg explains how normal cells can only double a certain limited number of times; and cancer cells have to learn how to proliferate indefinitely, i.e, they have to become immortalized.

Cells have a lifespan. The age of a cell and its ability to divide is related to structures – telomeres – found at the ends of chromosomes. Robert Weinberg, Ph.D., Whitehead Institute for Biomedical Research: “Normal cells can only double a certain limited finite number of times; cancer cells have to learn how to proliferate indefinitely, that i.e, they have to become immortalized. The machinery for controlling how often a cell may grow and divide, how many generations a lineage of cells may pass through, is carried in the telomeric DNAs at the ends of chromosomes. The telomeres are specialized sequences at the ends of each chromosome and they operate to prevent end-to-end fusion of chromosomes. These telomeres protect the ends of chromosomal DNA from such accidents. And as was learned in a number of laboratories, when normal cells go through cycles of growth and division their telomeric DNA gets shorter and shorter and shorter and ultimately so short it can no longer protect the ends of chromosomal DNA. Telomeres start fusing. Chromosomes start fusing in those cells, and those cells die. Cancer cells must avoid that problem because they want to grow indefinitely, and what do they do? They turn on an enzyme called telomerase that is normally expressed only early in embryologic development and in a small number of so-called stem cells in the body. The telomerase enzyme is able to extend the telomeres, making them longer and longer thereby enabling the cancer cell to go through many, many cycles of growth and division without worrying about the imminent collapse of its telomeres. The telomerase ensures the telomeres stay very long.” In 2000, Douglas Hanahan (shown below) and Robert Weinberg published a paper in Cell, "The Hallmarks of Cancer," which identified some organizing principles of cancer cell development. ”The nature of the replication machinery is that chromosomes get smaller every time they divide. And we now appreciate that specialized cells in the body have a way to counteract this telomere shorting and that’s using several strategies of which the most prominent is an enzyme known as telomerase that protects the ends of chromosomes from this erosion.”

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  • ID: 945
  • Source: DNALC.IC

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