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MOLECULAR BIOLOGY OF CANCER

Helga Burns
1993 Woodrow Wilson Biology Institute

Highlights Of Lecture By Arnold Levine, Princeton University MOLECULAR BIOLOGY OF CANCER

Cancer is defined as the loss of cell division control. This is a "Darwinian Problem" of competition in which the cancer cells will take over the normal function. It has been determined that it takes 5-6 mutations in one cell to cause cancer to occur.

This growth curve is an exponential curve, the exponent being 5.5 independent events to cause cancer. In the case of children fewer mutations are necessary.

graphic

Growth curve of Cancer

Those who develop cancer from 30-40 years of age probably inherited a pre-disposition to cancer that allows the cells to develop cancerous conditions with fewer mutations.

By 1985 the two types of cancer were determined:

Oncogenes

  • positive regulators (+ regulators)
  • cause acceleration of cell division dominant gene as well as wild type (find both wild type and mutant)
  • gain a new function fatal to fetal development

    • Tumor Suppressor Genes

  • negative regulators ( - regulators)
  • like having two brakes, both of them ON
  • recessive gene (find only this one gene, so both genes must mutate)
  • causes loss of function
  • silent in the fetus (if not essential)

    • Examples of Oncogenes that have been found work in tissues. 

    sis     Simian Sarcoma      PDGF stimulation
ras     Rat Sarcoma         effects G protein
erb-B   Chicken             affects growth receptor sites
        erthroblastosis
src     Rous sarcoma        Protein kinases cause 
                            signals in the S phase
myc     Myoblastic          affects while blood cells
        leukemia
    Examples of Tumor suppressor genes; those that cause negative regulation.

    "p53"

    found to be the single most common factor in cancer in mice. 65% of the cases have had this factor. Both genes must have mutated. Found on chromosome 17.

    fap

    familial adeno polyposis in the intestine which are pre-cancerous.

    Rb

    retinoblastoma. This is an example of the difference between inherited cancer and development of cancer. In some families a gene is passed on in which the babies develop 2,3 tumors per eye in both eyes. If a child develops the cancer a little later and only gets one tumor in one eye, he probably developed that cancer, and did not inherit it.

    graphic

    SKIN - any of these cell types can cause cancer.

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