Cancer
-Abnormal regulation of genes that affect the cell cycle can lead to cancer
-The genes that affect the cell cycle are also closely linked to embryonic
development and the maintenance of stem cell populations
-Types of genes associated with cancer
-Mutations in any genes that regulate cell growth/division, growth factors,
and cell signaling pathways can lead to cancer
-Additionally, cancer causing mutations result from environmental influences
-Oncogene: cancer causing gene
-Proto-oncogene: the normal/healthy version of an oncogene
-Usually stimulate normal cell growth and division
-Three genetic changes that convert proto-oncogenes to oncogenes:
1. Movement of DNA within the genome
-If a proto-oncogene is moved closer to an especially active
promoter, its transcription may increase
2. Amplification of a proto-oncogene
-Increases the number of copies of the proto-oncogene in the
cell through repeated gene duplication
3. Point mutations in a control element or in the proto-oncogene itself
-A point mutation in the promoter or enhancer may increase
the gene’s expression
-A point mutation in the gene itself may change the product to
a protein that is more active
-Tumor-suppressor gene: encodes proteins that help prevent uncontrolled
cell growth
-A mutation that harms a tumor-suppressor gene may stimulate cell
growth and division through the absence of normal suppression
-Interference with cell-signaling pathways
-The proteins encoded by many proto-oncogenes and tumor-suppressor
genes are components of cell-signaling pathways. Two examples:
1. ras proto-oncogene
-The Ras protein is encoded by the ras gene. It is a G protein
that relays a signal from a growth factor receptor on the
plasma membrane to a cascade of protein kinases that bring
the signal to the nucleus. This signaling cascade causes the
synthesis of a protein that stimulates the cell cycle.
-Certain mutations in the ras gene lead to the production of a
hyperactive Ras protein that interferes with the normal cell
signaling pathway and results in increased cell division
2. p53 tumor suppressor gene
-The p53 gene codes for a transcription factor that promotes
the synthesis of cell cycle-inhibiting proteins
-p53 is activated by DNA damage; it prevents a cell from
passing on mutations due to DNA damage
-A mutation in the p53 gene can lead to excessive cell growth
and division
-Multistep Model of Cancer Development
-About a half a dozen somatic mutations are generally needed for a cell to
become fully cancerous
-The development of a malignant tumor is caused by a gradual accumulation
of mutations that convert proto-oncogenes to oncogenes and knock out
tumor-suppressor genes
-Mutant tumor-suppressor genes are recessive, so two affected alleles must
be present to block tumor suppression
-Oncogenes behave as dominant alleles; only one affected allele is necessary
-Cancer treatments are becoming more personalized based on the genetic
and molecular characteristics of an individual’s tumor
1. Loss of tumor suppressor gene APC and activation of ras oncogene
2. Loss of tumor suppressor gene p53
3. Cancer does not actually form until many mutations occur
4. Metastasis requires even further genetic abnormalities
-Inherited predisposition and other factors contributing to caner
-Cancers can run in families
-An individual inheriting an oncogene or the mutant allele of a tumorsuppressor gene is one step closer to accumulating the necessary mutations
for cancer to develop
-Geneticists are working to be able to identify inherited cancer alleles; this
will cut down on the rate of cancer development of the most common
cancers (colorectal and breast cancers)
-DNA breakage contributes to cancer, which is why cancer risk can be
lowered by minimizing exposure to DNA-damaging elements
(mutagens/carcinogens)
-Cancer can also be caused by tumor-viruses
-Viruses interfere with gene regulation when they integrate their
genetic material into the DNA of a cell, donate an oncogene to the cell,
disrupt tumor-supressor genes, or convert proto-oncogenes into
oncogenes
-Ex. HPV, Epstein-Barr