The diagram below shows what cells look like when they are grouped together. Different types of body cells make up the different types of body tissues. For example, there are bone cells in bone and breast cells in the breast. You can read about different types of cells and cancer. Body tissues grow by increasing the number of cells that make them up.
Cells in many tissues in the body divide and grow very quickly until we become adults. When we are adults many cells mature and become specialised for their particular job in the body. So they don't make copies of themselves reproduce so often. But some cells, such as skin cells or blood cells are dividing all the time.
When cells become damaged or die the body makes new cells to replace them. This process is called cell division. One cell doubles by dividing into two.
Two cells become four and so on. The diagram below shows cells dividing. Stem cells provide a pool of dividing cells that the body uses to restock damaged or old cells. They have the potential to develop into different cell types in the body.
When a stem cell multiplies, the resulting cells may remain as stem cells. But under the right conditions, they become a type of cell with a more specialised function. For example a muscle cell, red blood cell or brain cell. Here we focus on the transformation assay, which scientists first used to identify oncogenes and tumor suppressors and study their affect on cell cycle progression. Even more important will be understanding the specific sequence of events in which multiple oncogenes and tumor suppressors must act in combination to promote cancerous cell growths Kinzler ; Hahn As early as , Peyton Rous demonstrated through his studies of tumorous growths in chickens that the potential for tumor generation could be transferred from animal to animal in cell-free extracts.
These extracts were eventually shown to contain viruses, whose ability to promote abnormally increased cell division in their hosts served to enhance their own replication. Thus the same processes stimulated by viral replication could lead to tumor production. This field of tumor virology was instrumental in developing the "cellular transformation assay" still used today to assess tumor growth.
Figure 2: Transformed cells exhibit different growth characteristics than non-transformed cells. Non-transformed cells panels A and B require a growing surface and experience contact inhibition to prevent crowding.
On the contrary, transformed cells panel C do not require a growing surface, and form high-density colonies called foci. Ghaleb, et al. Oncogene 28, All rights reserved. How do transformed cells grow? First, they no longer require contact with the surface of a culture dish. The transformed cells are, instead, capable of replicating in agar or in suspension Figure 2. This ability reflects a cancer cell's enhanced mobility, its ability to break down substances around it in order to create more space to grow and divide, and a reduction in the contact inhibition that normally prevents the cells from becoming too crowded.
Second, transformed cells will grow in more than one layer, producing abnormally abundant layers of cells. While untransformed cells grow parallel in orientation to one another in a single layer, transformed cells will pile up in chaotic fashion Figure 1. This feature is reminiscent of cancer cells that have reduced contact inhibition of growth. A third characteristic of transformed cells is their requirement for fewer nutrients in the media. This reflects tumor cells' ability to grow and divide even in the absence of growth factors.
Finally, transformed cells overcome the restriction of limited rounds of replication seen in normal cells and essentially become immortal Varmus Researchers made use of these results from early virology studies with cellular assays. In these experiments, they infected the cultured cells with various viruses and then looked for "transformations" to occur Todaro Since viral genomes are relatively small, researchers could more easily determine the genetic components responsible for transformation.
In fact, the first oncogenes they identified were derived from viruses and called viral oncogenes. Remarkably, researchers soon also realized that the source of these viral oncogenes came from cellular counterparts that had been transferred by viruses from one cell to another Varmus Figure 3: Cell cycle control by tumor suppressors and oncogenes Checkpoints are depicted as thick red bars. Tumor suppressors act to maintain checkpoints arrows whereas oncogenes allow for checkpoints to be overcome stop lines Adapted from Kopnin Figure Detail What, then, are oncogene products?
These are the proteins involved in cell cycle regulation that operate by stimulating cellular growth and division Figure 3. A common analogy equates oncogenes to an automobile's gas pedal stuck in the acceleration mode. Though the driver does not have his foot on the pedal, the car continues to speed up. Likewise, oncogenes code for proteins that function to drive the cell cycle forward, typically causing cells to proceed from one of the G gap phases to either chromosome replication S phase or chromosome segregation mitosis.
Examples include receptors at the cell surface that bind to growth factors, proteins that interact with DNA to initiate replication, and signaling molecules that link the receptors to the replication initiators through various pathways. In their normal state, genes that code for the normal proteins controlling these critical processes are called proto-oncogenes.
However, once they are altered see below to become oncogenes, their abnormal protein products exhibit increased activity that contributes to tumor growth. Therefore, instead of stopping within a G phase as it normally should, a tumor cell continues to progress through subsequent phases of the cell cycle, leading to uncontrolled cell division.
In addition, oncogenes can also rescue cells from programmed cell death. How does a proto-oncogene become converted to an oncogene? Figure 4 Occasionally, mutations will permanently activate proteins that normally interchange between active or inactive states. For example, Ras proteins function as molecular switches that are turned on and off depending on the form of nucleotide di-phosphate or tri-phosphate to which it is bound.
In an "on" state, the products of these proto-oncogenes relay proliferation-stimulating signals. Problems arise, however, when mutations convert the proto-oncogene to an oncogene, rendering Ras permanently active regardless of the signals the cell receives.
Figure 4: Three major types of genetic alterations leading to oncogene activation. The proto-oncogene top is depicted as a regulatory sequence RS followed by the coding region gene. In the first example, a star indicates the location of the nucleotide substitution on the transcribed portion of the gene. In the case of the translocation example, a different regulatory sequence becomes responsible for stimulating transcription of a resultant fusion protein.
For the amplification example, the presence of multiple copies of the gene results in excessive expression Adapted Kufe et al. Figure Detail A second type of genetic alteration that converts a proto-oncogene to an oncogene is a chromosomal translocation. This occurs when the pieces of broken chromosomes reattach haphazardly, leading either to the formation of a fusion protein containing the N-terminus of one protein and the C-terminus of another, or leading to altered regulation of protein expression Figure 4.
Cellular Senescence Most cells also seem to have a pre-programmed limit to the number of times that they can divide. Interestingly, the limit seems to be based, in part, on the cell's ability to maintain the integrity of its DNA. An enzyme , telomerase , is responsible for upkeep of the ends of the chromosomes. In adults, most of our cells don't utilize telomerase so they eventually die. In cancer cells, telomerase is often active and allows the cells to continue to divide indefinitely.
For more information on telomerase, see the Cancer Genes section. Continued cell division leads to the formation of tumors. The genetic instability that results from aberrant division contributes to the drug resistance seen in many cancers. Mutations in specific genes can alter the behavior of cells in a manner that leads to increased tumor growth or development. Providing reliable information about cancer biology and treatment.
Cell Division During a lifetime, many of the cells that make up the body age and die. Reasons that cells are lost and must be replaced include the following: Sloughing off of epithelial cells such as those lining the skin and intestines.
The old, worn out cells on the surface of the tissues are constantly replaced. A special case of this is the monthly replacement of the cells lining the uterus in pre-menopausal women. Wound healing requires that cells in the area of the damage multiply to replace those lost. Viral diseases such as hepatitis may also cause damage to organs that then need to replace lost cells. Replacement of the cells that make up blood. Childhood Cancers Research.
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Cancer is a disease caused when cells divide uncontrollably and spread into surrounding tissues.
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