Ch. 20 Genetics of Cancer
Occasionaly, dividing and differentiating cells derivate from their normal and genetic program and give
rise to tissue masses called tumors or neoplasms,
-the process by which a cell loses its ability to remain constrained in its growth properties is called
-if transformed cells stay together in a single mass, the tumor is said to benign.
-this phenomenon is brought about by contact inhibition, a process whereby cells in contact
communicate with one another and cell division is stopped. Contact inhibition is reflective of the
regulated nature of cell division shown by normal cells. By contrast, transformed cells do now show
contact inhibition, instead continuing to grow and divide after contacting neighbors and piling up in
-if the cells of a tumor can invade and disrupt surrounding tissues, tumor is said to be malignant and is
identified as cancer
-metastasis: the spreading of malignant tumor cells throughout the body. Sometimes, cells from
malignant tumors can break off and move throughout the blood or lymphatic system, forming new
tumors at other locations in the body
-The initiation of tumors in an organisms called oncogenesis
Relationship of the cell cycle to cancer
-cells that cant divide anymore: terminally differentiated cells
-have a finite lifespan. And are replaced with younger cells produced by division of unspecialized
cells called stem cells (which are a small fraction of cells in the tissue that are capable of self-renewal)
Molecular control of the cell cycle
-checkpoints at different points in the cell cycle are control points at which the cell cycle is arrested if
there is damage to genome or cell cycle machinery. This allows damaged to be repaired or if it can’t be
repaired then destroyed. Prevents creation of cancerous cells
- checkpoints include: in G 1o S checkpoint. Determines whether the cell is able or should continue from
G 1o S. G 2o M checkpoint.. A third checkpoint occurs during M.
-Proteins known as cyclins and enzymes known as cyclin-dep. kinases (Cdks) are the key components in
the regulatory events that occur at checkpoints
Regulation of Cell Division in Normal Cells
--the extracellular molecules are steroids and polypeptide hormones made in other tissues that
influence the growth and division of cells in other tissues.
-Signal transduction: the process of relaying a growth stimulatory or growth inhibitory signal after an
extracellular binds to a cell
-Normal, healthy cells give rise to progeny cells only when the balance of stimulatory and inhibitory
singals from outside the cell favors cell division.
-A neoplastic cell (tumor), on the other hand, has lost control of the cell division and reproduces without
-this can occur when genes either for stimulatory factors, inhibitory factors, or signal transduces
mutate, or when genes encoding cell surface receptors or signal transducers involved in cell cycle are
Cancers are Genetic Diseases
-several lines of evidence that indicate that cancer are genetic disorders
-There is a high incidence of particular cancer in some human families. Cancers that run in
families are known as familial (hereditary) cancers; cancers that do not appear to be inherited are known as sporadic (nonhereditary) cancers. Sporadic cancers are more frequent than are familial
-some viruses can induce cancer. This means that expression of viral genes introduced into the
hose is able to disrupt normal cell cycle controls
-descendants of cancerous cells are all cancerous. In fact, it is the clonal descendants of a cell
that become cancerous forming.
-the incidence of cancers increases upon exposure to mutagenic agents.
-certain chromosomal mutations are associated with particular forms of cancer.
Genes and Cancer
-four main classes of genes are altered in cancer:
-proto-oncogenes, tumor suppressor genes, microRNA (miRNA) genes, and mutator genes.
-the products of proto-oncogenes normally stimulate cell proliferation. Mutant proto-oncogenes called
oncogenes (found in cancer cells), are either more active than normal or active at inappropriate times.
-the products of unmutated tumor suppressor genes normally inhibit cell proliferation. Mutant tumor
suppressor genes found in cancer cells have lost their inhibitory function.
-The products of normal miRNA genes target mRNAs encoded by other genes and inhibit their
translation; some of the genes whose expression are silenced in this way are involved in proliferation.
Overexpressed miRNA genes act as oncogenes, while under expressed miRNA genes act as defective
tumor suppressor genes
-the products of wild-type mutator genes are needed to ensure fidelity of replication and maintenance
of genome integrity. Mutant mutator genes in cancer cells have lost their normal function, and this
makes the cell prone to accumulate mutational error in any gene, including proto-oncogenes and tumor
-transformation of cells to the neoplastic state can result from infection with tumor viruses (all
retroviruses), which induce the cells they infect to proliferate in an uncontrolled fashion and produce a
-ONCOGENE (definition): a gene whose action stimulates unregulated cell proliferation
-all tumor viruses are retroviruses
-distinct feature of a retrovirus is that, once it infects a cell the single-stranded RNA genome is
converted to a double stranded proviral DNA. The proviral DNA integrates into a chromosome of the
host and directs the generation of progeny retroviruses
Life cycle of retroviruses
-when the retrovirus infects a cell, the RNA genome is released from the viral particle, and reverse
transcriptase, an enzyme brought into th