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UNIT 1
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the proportion of dividing cells

• mitotic index may be elevated during processes that promote division, such as normal growth
or cellular repair

◦ functions as an important prognostic tool for predicting the response of cancer cells to
chemotherapy



Identifying Mitotic Cells

• cells undergoing mitosis will lack a clearly defined nucleus and possess visibly condemned
chromosomes

◦ prophase: chromosomes condensed but still confined to a nuclear region

◦ metaphase: chromosomes aligned along the equator of the cell

◦ anaphase: two distinct clusters of chromosomes apparent at poles of the cell

◦ telophase: two nuclear present within a single cell (difficult to see as cytokinesis occurs
concurrently)



Calculating Mitotic Cells

• the mitotic index is the ratio between the number of cells in mitosis and the total number of
cells

• can be determined by analyzing micrographs and counting the relative number of mitotic cells
versus non-diving cells



Cyclins:

Mechanisms of Cyclin Action

• cyclins are a family of regulatory proteins that control the progression of the cell cycle

• cyclins activate cyclin dependent kinases (CDKs), which control cell cycle processes through
phosphorylation

• the phosphorylated target protein will trigger some specific event within the cell cell cycle

◦ e
...
centrosome duplication

• after the event has occurred, the cyclin is degraded and the CDK is rendered inactive again





Cyclin Expression Patterns

• cyclin concentrations need to be tightly regulated in order to ensure the cell cycle progresses
in a proper sequence

◦ different cyclins specifically bind to, and activate, different classes of cyclin dependent
kinases

◦ cyclin levels will peak when their target protein is required for function and remain at lower
levels at all other times



Cancer Development
• tumors are abnormal cell growths resulting from uncontrolled cell division and can occur in any
tissue or organ

◦ disease caused by the growth of tumors are collectively known as cancers



Mutagens

• mutagen is an agent that changes the genetic material of an organism (either acts on the DNA
or the replicative machinery)

• mutagens may be physical, chemical or biological in origin:

◦ physical: sources of radiation including x-rays (ionizing), ultraviolet (UV) light and
radioactive decay

◦ chemical: DNA interacting substance including reactive oxygen species (ROS) and metals

‣ e
...
arsenic

◦ biological: viruses, certain bacteria and mobile genetic elements

‣ transposons

• mutagens that lead to the formation of cancer are further classified as carcinogens



Oncogenes

• an oncogene is a gene that has the potential to cause cancer

• most cancers are caused by mutations to two basic classes of genes - photo-oncogenes and
tumor suppressor genes

◦ proto-oncogenes code for proteins that stimulate the cell cycle and promote cell growth
and proliferation

◦ tumor suppressor genes code for proteins that repress cell cycle profession and promote
apoptosis

• when a porto-oncogene is mutated or subjected to increased expression it becomes a cancercausing oncogene

• tumor suppressor genes are sometimes referred to as anti-oncogenes, as their normal function
prevents cancer



Relationship between Proto-Oncogenes and Tumor Suppressor Genes






Metastasis

• tumor cells may either remain in their original location (benign) or spread and invade
neighboring tissue (malignant)

• metastasis is the spread of cancer from one location (primary tumor) to another, forming a
secondary tumor

• secondary tumors are made up of the same type of cells as the primary tumor - this affects the
type of treatment required

◦ e
...
if breast cancer spread to the liver, the patient has secondary breast cancer of the
liver (treat with breast cancer drugs)



Smoking and Cancer
• significant body of scientific literature exist which provides a strong link between smoking and
the incidence of cancers

◦ cigarette smoke contains over 4,000 chemical compounds, over 60 of which are known to
be carcinogenic

• there appears to be a strong positive correlation between the frequency of smoking and the
development of cancer

◦ risk of lung cancer is strongly correlated with smoking, with ~90% of lung cancers
attributable to tobacco use

◦ smoking also increases the risk of over a dozen other cancers, including mouth, stomach,
liver, pancreas and bowel




































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