Cancer comprises many different diseases caused by a common mechanism: uncontrolled cell growth.
Cancer is the result of unchecked cell division caused by a breakdown of the mechanisms that regulate the cell cycle. The loss of cell cycle control begins with a DNA sequence change of a gene that codes for one of the regulatory molecules, known as a mutation. Faulty instructions lead to a protein that does not function normally. Each successive cell division will give rise to daughter cells with even more accumulated damage. Eventually, all checkpoints become non-functional, and rapidly reproducing cells that push out healthy cells, resulting in a tumor or leukemia (blood cancer).
Proto-oncogenes normally regulate cell division but can be changed into oncogenes through mutation, which may cause cancers to form. Proto-oncogenes positively regulate the cell cycle, whereas oncogenes disrupt normal cell division and cause cancers to form. Some mutations prevent the cell from reproducing, which keeps the mutations from being passed on. If a mutated cell is able to reproduce because the cell division regulators are damaged, then the mutation will be passed on, possibly accumulating more mutations with successive divisions.
Tumor suppressor genes are segments of DNA that code for negative regulator proteins, which keep the cell from undergoing uncontrolled division. One of the most important tumor suppressors is tumor protein p53, which plays a vital role in the cellular response to DNA damage. The role of normal p53 is to monitor DNA and the supply of oxygen (hypoxia is a condition of reduced oxygen supply). If damage is detected, p53 triggers repair mechanisms. If repairs are unsuccessful, p53 signals apoptosis.
A cell with an abnormal p53 protein cannot repair damaged DNA and thus cannot signal apoptosis. Without a fully functional p53, the G1 checkpoint of interphase is severely compromised and the cell proceeds directly from G1 to S; this creates two daughter cells that have inherited the mutated p53 gene. Mutated p53 genes are believed to be responsible for causing tumor growth because they turn off the regulatory mechanisms that keep cells from dividing out of control. Cells with abnormal p53 can become cancerous.
Practice Questions
Khan Academy
- Myelogenous leukemia and two chemotherapeutic agents
- A genetic mutation with prognostic value for glioblastoma patients
Key Points
• Proto-oncogenes positively regulate the cell cycle.
• Mutations may cause proto-oncogenes to become oncogenes, disrupting normal cell division and causing cancers to form.
• When genes that produce regulator proteins become mutated, it creates a malformed and non-functional, cell-cycle regulator that increases the chance of more mutations in the cell.
• A tumor suppressor gene is a segment of DNA that codes for the negative cell-cycle regulators; if that gene becomes mutated to an underactive form, the cell cycle will run unchecked.
• Mutated p53 genes are responsible for causing tumor growth because they turn off the regulatory mechanisms that keep cells from dividing out of control.
Key Terms
mutation: any heritable change of the base-pair sequence of genetic material
proto-oncogene: a normal gene that when mutated becomes an oncogene
oncogene: a mutated version of a normal gene involved in the positive regulation of the cell cycle
tumor suppressor gene: a segment of DNA that codes for regulator proteins that prevent the cell from undergoing uncontrolled division
apoptosis: a process of programmed cell death
G1 checkpoint: a point in the animal cell cycle at which the cell becomes “committed” to the cell cycle, which is determined by external factors and signals
p53: cell cycle regulatory protein that regulates cell growth and monitors DNA damage; it halts the progression of the cell cycle in cases of DNA damage and may induce apoptosis