2012 Bio 314 Chapter 10

2012 Bio 314 Chapter 10 - The Biology of Cancer First...

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Unformatted text preview: The Biology of Cancer First Edition Chapter 10: Eternal Life: Cell Immortalization and Tumorigenesis Copyright Garland Science 2007 Robert A. Weinberg Immortalization and Tumorigenesis Normal cells are mortal; they have a fixed number of growth division cycles, then they permanently stop dividing. Tumor cells are immortal, they have an infinite number of growth division cycles. This must be the case, as it takes multiple growth division cycles to acquire the successive genetic changes necessary for tumorigenesis. 10. 1 Normal cell populations register the number of cell generations separating them from their ancestors in the early embryo This phenomenon has been well characterized in Caenorhabditis elegans , a simple roundworm. The adult is composed of 959 cells, and the lineage of each cell has been determined by observation. Adult humans have 1014 cells, so a comparable lineage map can exist only in theoretical terms. Figure 10.1a The Biology of Cancer ( Garland Science 2007) C. elegans ; a model system for growth, differentiation, apoptosis. http://www.wormatlas.org/ http://www.bio.unc.edu/faculty/goldstein/lab/movies.html http://nobelprize.org/nobel_prizes/medicine/laureates/2002/illpres/introduction.html The pedigree of cells in the body of a worm Figure 10.2 The Biology of Cancer ( Garland Science 2007) The proliferative capacity of cells (human fibroblasts) in tissue culture. {Primary cells vs cell lines.} Serial passaging Figure 10.3 The Biology of Cancer ( Garland Science 2007) Senescent cells (right) are viable and metabolically active but have irreversibly ceased replication. They continue to express growth factor receptors, and apparently require growth factors for survival, but they no longer proliferate in response to mitogenic signaling. The downstream signaling pathways have been inactivated. What happens in vivo in complex multicellular organisms ? Early in embryogenesis, cells have unlimited replicative ability. With the establishment of specific cell lineages, cells are given a pre-determined replicative potential. The loss of proliferative capacity with age is a frequent observation in multiple cell types, multiple organisms, in vivo and in vitro. Why? Is it a defense mechanism against cancer, to ensure that a potentially neoplastic cell does not have enough replicative potential left to cause serious harm? Figure 10.4b The Biology of Cancer ( Garland Science 2007) Keratinocytes have lost the ability to proliferate and cannot regenerate the entire layer, so skin becomes thinner and less firm with age. 10.2 Cancer cells need to become immortal in order to form tumors Loss of proliferative capacity with age Figure 10.5a The Biology of Cancer ( Garland Science 2007) If cell number actually doubled with each generation, 40 generations would be more than enough for a life-threatening tumor....
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2012 Bio 314 Chapter 10 - The Biology of Cancer First...

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