Checkpoints and Control of the Cell Cycle

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					                      Checkpoints and Control of the Cell Cycle

Cell growth and cell division are strictly controlled in multicellular organisms. They are
regulated both internally and externally by proteins.

External Regulators

Proteins that respond to events outside the cell are called external regulators. External
regulators direct the cell to speed up or slow down the cell cycle. ie: growth factors

Internal Regulators

Proteins that respond to events inside the cell are called internal regulators. Internal
regulators allow the cell to cycle to proceed only when certain processes have happened
inside the cell. The cell has several systems for interrupting the cell cycle if there is a
problem. These control systems are celled checkpoints. Checkpoints are biological
stoplights telling the cell when it can safely go or when to stop and fix a problem. There
are 3 checkpoints which consists of:

      the G1 checkpoint: makes sure the cell is large enough to enter the S phase, that
       nutrient availability is sufficient, and that growth factors from other cells are

      the G2 checkpoint: makes sure the DNA is completed replicated, that errors have
       been repaired, and that the cell is large enough to divide.

      the Metaphase checkpoint: makes sure the chromosomes are aligned on the
       spindle, ready for cell division.
                           Cancer: Uncontrolled Cell Growth

In cancer cells, some or all of the usual checkpoints fail, leading to an over proliferation
of abnormal cells. The faulty checkpoints make the cell unable to check if DNA
replication was complete, if any mutations need to be repaired, if the DNA was properly
separated between the daughter cells, or any other problems. The cells are likely to
become cancerous with their multiple genomic problems.

Cancer cells usually group or clump together to form tumors. A growing tumor becomes
a lump of cancer cells that can destroy the normal cells around the tumor and damage the
body's healthy tissues. Sometimes cancer cells break away from the original tumor and
travel to other areas of the body, where they keep growing and can go on to form new
tumors. This is how cancer spreads. The spread of a tumor to a new place in the body is
called metastasis.

p53: Keeping Cancer in Check

The p53 protein is a tumor suppressor encoded by a gene whose disruption is associated
with approximately 50 to 55 percent of human cancers. The p53 protein “acts as a
checkpoint” in the cell cycle by preventing or initiating programmed cell death. Since
cancer is the unchecked proliferation of cells, p53's role is critical.

But if people have a built-in tumor suppressor, why do so many get cancer?

The p53 molecule can be inactivated in several ways. In some human families, p53
mutations are inherited, and family members have a high incidence of cancer. More
often, the molecule is inactivated by an outside source. DNA tumor viruses, such as the
human adenovirus and the human papilloma virus, can bind to and inactivate the p53
protein function, altering cells and initiating tumor growth. In addition, some sarcomas
amplify another gene, called mdm-2, which produces a protein that binds to p53 and
inactivates it.

The p53 tumor suppressor and its surrounding molecules are now the focus of thousands
of studies in laboratories around the world. These studies may one day lead to new
treatments for the most frequent and life-threatening of cancers.

Treating Cancer Carefully

Cancer is treated with surgery, chemotherapy, or radiation or sometimes a combination of
these treatments. The choice of treatment depends on the type of cancer and the stage of
the tumor. The typical treatments include: surgery, chemotherapy, and radiation.
Surgery is the oldest form of treatment for cancer. Three out of five people with cancer
will have an operation to remove it. During surgery, the doctor tries to take out as many
cancer cells as possible. Some healthy cells or tissue may also be removed to make sure
that all the cancer is gone.

Chemotherapy is a method of treating cancer by using one drug or a combination of
drugs. Chemotherapy works by slowing or stopping the cancer cells from growing,
spreading or multiplying to other parts of the body. Unlike surgery and radiotherapy
(radiation therapy treatments), which can target a specific area of the body, chemotherapy
drugs get carried throughout the patient’s body. These drugs can damage healthy cells in
addition to cancerous cells, which can cause many side effects. The body’s healthy cells
usually repair themselves after a period of rest from the chemotherapy.

A doctor may prescribe chemotherapy for a cancer patient to achieve any of five
treatment goals:

   1. to destroy the cancer. Chemotherapy can be used by itself or in combination with
      other treatments to cure many types of cancer.
   2. to shrink a tumour before other treatments. Sometimes surgery or radiation
      therapy is more successful if chemotherapy is used first to reduce the size of the
      cancer tumour.
   3. to destroy residual cancer cells after other treatments. Depending on the type of
      cancer, surgery and radiation therapy may not be able to remove all the cancer
      cells from the patient. Chemotherapy can be used as a follow-up to destroy any
      cancer cells that were missed.
   4. to prepare the patient for a bone marrow or stem cell transplant. Some cancers
      can be treated with bone marrow or stem cell transplants from a donor. Before the
      transplants take place, the cancer patient’s original bone marrow is destroyed
      using high doses of chemotherapy drugs.
   5. to relieve cancer symptoms (palliative chemotherapy). In some cases,
      chemotherapy can reduce the pain and other symptoms of cancer.

A person who has cancer may receive radiation therapy as a treatment. Radiation therapy
is also known as radiotherapy or x-ray treatment. Radiation therapy uses high-energy
waves to damage and destroy cancer cells. There are two main ways to give radiation
treatment: from the outside or from the inside. Radiation given from the outside involves
a person lying on a table, like having an x-ray taken, and a large machine moves around
them without touching them. The radiation travels out of the machine to the patient,
external to the patient. On the other hand, radioactive substances can be implanted,
inserted, injected or ingested into the body, and give off their radiation internally.
A doctor may prescribe radiation therapy for a cancer patient to achieve any of three
treatment goals:

   1. to destroy the cancer. Radiation can be used alone or in combination with other
      treatments to destroy cancer cells in the body with the intention of curing the
   2. to shrink a tumor. Radiation can be used to shrink a tumor before other
      treatments or can be used to reduce the chances of cancer returning after surgery.
   3. to relieve cancer symptoms. Radiation can also help decrease symptoms related
      to cancer, such as pain or difficulty with swallowing.

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