Cell division is highly regulated Cell division is highly regulated. The cell does not divide unless it receives the appropriate extracellular signals. Growth factors (hormones or polypeptides) stimulate growth. Cells also have proteins which come in contact with other cells. If the contact is lost, cell division is stimulated.

There are a variety of ways to stimulate cell growth There are a variety of ways to stimulate cell growth. One is for a growth factor to bind to receptors on the cell membrane (extracellular signaling), which triggers a series of events leading to cell division. A second type of signaling is called intracellular signaling. Cells grow until they are in contact with cells around them. When they touch, cell adhesion proteins attach the two cells. These adhesion proteins are transmembrane proteins which transmit a signal to stop growing when they contact another cell. If the neighboring cell dies or is destroyed by injury, the adhesion protein sends a signal to initiate growth and replace the lost cell.

Growth hormones have a specific shape and fit like a key only inside receptors which have the exact shape necessary. Because of this, hormones can be released from a distant location (like the brain) into the blood, and travel all over the body but only initiate growth of the desired cells. Small polypeptides can be released from cells into the extracellular fluid and stimulate growth locally.

Receptors are transmembrane proteins, with the binding site on the extracellular surface. When the hormone binds, the receptor changes shape, activating an enzyme located in the intracellular portion of the cell. Thus, the receptor converts a signal on the outside into a signal on the inside. The receptor enzyme will add a phosphate group onto a specific protein, activating that protein.

There are a number of pathways which are involved in activating (phosphorylating) or inactivating (dephosphorylating) proteins. This gives the cell many ways of controlling what is going on inside. One such pathway involves phospholipids which, when changed, alter the activity of specific proteins. A kinase is an enzyme which phosphorylates molecules.

Growth and cell division have to be closely regulated Growth and cell division have to be closely regulated. Therefore, there are many proteins involved in carrying the signal from the receptor to the nucleus where the genes regulating cell division can be activated. These proteins are called proto-oncogenes. The proto-oncogenes work in a specific sequence. When one is activated, it then activates the next one in line. Each proto-oncogene is a site of regulation Finally, a proto-oncogene is activated and now can enter the nucleus. This protein will bind to the DNA in the promoter site of a specific gene or a group of genes. When this occurs, the gene will be transcribed.

Tumor Suppressor Activity There is a second set of proteins known as tumor suppressors. These proteins function by inactivating (turning off) the proto-oncogenes. In essence, they are necessary to stop cell division. These proteins were discovered by scientists studying cancer. They found that when the genes for these proteins were activated, tumors did not develop when they gave mice carcinogens. That is, they suppressed tumor formation. Tumor Suppressor Activity

Tumor Suppressor Pathway Similar to proto-oncogenes, there are a number of tumor suppressors. Each tumor suppressor protein inactivates specific proto-oncogenes. By doing so, they shut off the signal which causes cells to divide. Tumor Suppressor Pathway

Proto-oncogenes are normal and necessary proteins Proto-oncogenes are normal and necessary proteins. If one of these genes &, therefore, proteins is mutated, it can become an oncogene (and cause cancer). How? When a proto-oncogene becomes activated, it will now modify & activate the next proto-oncogene in the sequence. All downstream proteins now become activated and cell division results. If the mutation results in a permanently activated proto-oncogene, it causes uncontrolled cell growth.

Liver Cancer Colon Cancer Lung Cancer As cancer cells continuously grow, they crowd out normal cells around them. Blood vessels are squeezed, shutting down the flow of oxygen and nutrients. Normal cells are killed. Cancer cells are able to survive, because they cause the growth of blood vessels feeding the cancer cells themselves. A new type of drug to treat cancer actually prevents the growth of these cancer-supplying blood vessels.

Skin Cancer

Colon Cancer

Skin Cancer

NEWS FLASH We have a natural defense against cancerous cells. It is our immune cells. Cancer cells often express abnormal proteins. These proteins are detected as foreign proteins and the cells are destroyed. In the picture, the tumor cell is killed by a T lymphocyte (white blood cell) which inserts a protein pore which allows cytoplasm to leak out, killing the cell.

REVIEW OF CELL GROWTH REGULATORY MECANISMS AND POSSIBLE WAYS THIS REGULATION IS LOST

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