Cancer results from a series of molecular events that fundamentally alter the normal properties of cells. In cancer cells the normal control systems that prevent cell overgrowth and the invasion of other tissues are disabled. These altered cells divide and grow in the presence of signals that normally inhibit cell growth; therefore, they no longer require special signals to induce cell growth and division. As these cells grow they develop new characteristics, including changes in cell structure, decreased cell adhesion, and production of new enzymes. These heritable changes allow the cell and its progeny to divide and grow, even in the presence of normal cells that typically inhibit the growth of nearby cells. Such changes allow the cancer cells to spread and invade other tissues.
The abnormalities in cancer cells usually result from mutations in
protein-encoding genes that regulate cell division. Over time more
genes become mutated. This is often because the genes that make the
proteins that normally repair DNA damage are themselves not
functioning normally because they are also mutated. Consequently,
mutations begin to increase in the cell, causing further abnormalities
in that cell and the daughter cells. Some of these mutated cells die, but
other alterations may give the abnormal cell a selective advantage that
allows it to multiply much more rapidly than the normal cells. This
enhanced growth describes most cancer cells, which have gained
functions repressed in the normal, healthy cells. As long as these cells
remain in their original location, they are considered benign; if they
become invasive, they are considered malignant. Cancer cells in
malignant tumors can often metastasize, sending cancer cells to distant
sites in the body where new tumors may form.
Alterations in the same gene often are associated with different forms of cancer. These malfunctioning genes can be broadly classified into three groups. The first group, called pro to-oncogenes produces protein products that normally enhance cell division or inhibit normal cell death. The mutated forms of these genes are called oncogenes. The second group, called tumor suppressors makes proteins that normally prevent cell division or cause cell death. The third group contains DNA repair genes, which help prevent mutations that lead to cancer.
Proto-oncogenes and tumor suppressor genes work much like the
accelerator and brakes of a car, respectively. The normal speed of a car
can be maintained by controlled use of both the accelerator and the
brake. Similarly, controlled cell growth is maintained by regulation of
proto-oncogenes, which accelerate growth, and tumor suppressor genes,
which slow cell growth. Mutations that produce oncogenes accelerate
growth while those that affect tumor suppressors prevent the normal
inhibition of growth. In either case, uncontrolled cell growth occurs. Oncogenes are
altered versions of the proto-oncogenes that code for these signaling
molecules. The oncogenes activate the signaling cascade continuously,
resulting in an increased production of factors that stimulate growth. RAS is an oncogene that normally
functions as an “on-off” switch in the signal cascade. Mutations in RAS
cause the signaling pathway to remain “on,” leading to uncontrolled
cell growth. About thirty percent of tumors — including lung, colon,
thyroid, and pancreatic carcinomas — have a mutation in RAS.
We also learned about the suppressor gene P53. Upon cellular stress, particularly that induced by DNA damage, p53 can arrest cell cycle progression, thus allowing the DNA to be repaired; or it can lead to apoptosis. These functions are achieved, in part, by the transactivational properties of p53, which activate a series of genes involved in cell cycle regulation. In cancer cells bearing a mutant p53, this protein is no longer able to control cell proliferation, resulting in inefficient DNA repair and the emergence of genetically unstable cells. The most common changes of p53 in human cancers are point missense mutations within the coding sequences of the gene.
Alterations in the same gene often are associated with different forms of cancer. These malfunctioning genes can be broadly classified into three groups. The first group, called pro to-oncogenes produces protein products that normally enhance cell division or inhibit normal cell death. The mutated forms of these genes are called oncogenes. The second group, called tumor suppressors makes proteins that normally prevent cell division or cause cell death. The third group contains DNA repair genes, which help prevent mutations that lead to cancer.
We also learned about the suppressor gene P53. Upon cellular stress, particularly that induced by DNA damage, p53 can arrest cell cycle progression, thus allowing the DNA to be repaired; or it can lead to apoptosis. These functions are achieved, in part, by the transactivational properties of p53, which activate a series of genes involved in cell cycle regulation. In cancer cells bearing a mutant p53, this protein is no longer able to control cell proliferation, resulting in inefficient DNA repair and the emergence of genetically unstable cells. The most common changes of p53 in human cancers are point missense mutations within the coding sequences of the gene.
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