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By the end of this section, you will be able to:
  • Explain how cancer is caused by uncontrolled cell division
  • Understand how proto-oncogenes are normal cell genes that, when mutated, become oncogenes
  • Describe how tumor suppressors function to stop the cell cycle until certain events are completed
  • Explain how mutant tumor suppressors cause cancer

Cancer is a collective name for many different diseases caused by a common mechanism: uncontrolled cell division. Despite the redundancy and overlapping levels of cell-cycle control, errors occur. One of the critical processes monitored by the cell-cycle checkpoint surveillance mechanism is the proper replication of DNA during the S phase. Even when all of the cell-cycle controls are fully functional, a small percentage of replication errors (mutations) will be passed on to the daughter cells. If one of these changes to the DNA nucleotide sequence occurs within a gene, a gene mutation results. All cancers begin when a gene mutation gives rise to a faulty protein that participates in the process of cell reproduction. The change in the cell that results from the malformed protein may be minor. Even minor mistakes, however, may allow subsequent mistakes to occur more readily. Over and over, small, uncorrected errors are passed from parent cell to daughter cells and accumulate as each generation of cells produces more non-functional proteins from uncorrected DNA damage. Eventually, the pace of the cell cycle speeds up as the effectiveness of the control and repair mechanisms decreases. Uncontrolled growth of the mutated cells outpaces the growth of normal cells in the area, and a tumor can result.

Proto-oncogenes

The genes that code for the positive cell-cycle regulators are called proto-oncogenes . Proto-oncogenes are normal genes that, when mutated, become oncogenes —genes that cause a cell to become cancerous. Consider what might happen to the cell cycle in a cell with a recently acquired oncogene. In most instances, the alteration of the DNA sequence will result in a less functional (or non-functional) protein. The result is detrimental to the cell and will likely prevent the cell from completing the cell cycle; however, the organism is not harmed because the mutation will not be carried forward. If a cell cannot reproduce, the mutation is not propagated and the damage is minimal. Occasionally, however, a gene mutation causes a change that increases the activity of a positive regulator. For example, a mutation that allows Cdk, a protein involved in cell-cycle regulation, to be activated before it should be could push the cell cycle past a checkpoint before all of the required conditions are met. If the resulting daughter cells are too damaged to undertake further cell divisions, the mutation would not be propagated and no harm comes to the organism. However, if the atypical daughter cells are able to divide further, the subsequent generation of cells will likely accumulate even more mutations, some possibly in additional genes that regulate the cell cycle.

The Cdk example is only one of many genes that are considered proto-oncogenes. In addition to the cell-cycle regulatory proteins, any protein that influences the cycle can be altered in such a way as to override cell-cycle checkpoints. Once a proto-oncogene has been altered such that there is an increase in the rate of the cell cycle, it is then called an oncogene.

Tumor suppressor genes

Like proto-oncogenes, many of the negative cell-cycle regulatory proteins were discovered in cells that had become cancerous. Tumor suppressor genes are genes that code for the negative regulator proteins, the type of regulator that—when activated—can prevent the cell from undergoing uncontrolled division. The collective function of the best-understood tumor suppressor gene proteins, retinoblastoma protein (RB1), p53, and p21, is to put up a roadblock to cell-cycle progress until certain events are completed. A cell that carries a mutated form of a negative regulator might not be able to halt the cell cycle if there is a problem.

Mutated p53 genes have been identified in more than half of all human tumor cells. This discovery is not surprising in light of the multiple roles that the p53 protein plays at the G 1 checkpoint. The p53 protein activates other genes whose products halt the cell cycle (allowing time for DNA repair), activates genes whose products participate in DNA repair, or activates genes that initiate cell death when DNA damage cannot be repaired. A damaged p53 gene can result in the cell behaving as if there are no mutations ( [link] ). This allows cells to divide, propagating the mutation in daughter cells and allowing the accumulation of new mutations. In addition, the damaged version of p53 found in cancer cells cannot trigger cell death.

This illustration shows cell cycle regulation by p53. The p53 protein normally arrests the cell cycle in response to DNA damage, cell cycle abnormalities, or hypoxia. Once the damage is repaired, the cell cycle restarts. If the damage cannot be repaired, apoptosis (programmed cell death) occurs. Mutated p53 does not arrest the cell cycle in response to cellular damage. As a result, the cell cycle continues and the cell may become cancerous.
(a) The role of p53 is to monitor DNA. If damage is detected, p53 triggers repair mechanisms. If repairs are unsuccessful, p53 signals apoptosis. (b) A cell with an abnormal p53 protein cannot repair damaged DNA and cannot signal apoptosis. Cells with abnormal p53 can become cancerous. (credit: modification of work by Thierry Soussi)

Concept in action

Go to this website to watch an animation of how cancer results from errors in the cell cycle.

Section summary

Cancer is the result of unchecked cell division caused by a breakdown of the mechanisms regulating the cell cycle. The loss of control begins with a change in the DNA sequence of a gene that codes for one of the regulatory molecules. Faulty instructions lead to a protein that does not function as it should. Any disruption of the monitoring system can allow other mistakes to be passed on to the daughter cells. Each successive cell division will give rise to daughter cells with even more accumulated damage. Eventually, all checkpoints become nonfunctional, and rapidly reproducing cells crowd out normal cells, resulting in tumorous growth.

Questions & Answers

now that we have an estimate for the diameter of the cell.what estimate can we make about the volume of the cell?
faxhood Reply
why too much insulin result in low blood sugar
Leri Reply
difference between DNA and RNA
Eyitayo Reply
DNA is deoxyribonuclaic acid. Deoxy refers to a lack of oxygen. The Ribose moity is missing an OH group. I think it is missing from the second C of the ring. RNA is ribonucleic acid. DNA has our genetic code in on it. RNA is translated from DNA and carries the blue print for protein synthesis.
Eric
The OH group on RNA prevents it from being reactive. But it is very unstable though. Would you want such a power tool floating around in your body, no. And you have three types of RNA: mRNA, tRNA and rRNA. Please let me know it this helped?😄
Eric
o
Browse
what determines the aeration level in the soil
Shola Reply
what is homeostasis?
Sarita Reply
What is biology
Don Reply
Biology z the study of life
GOLDEN
what's biology
buran
biology is the study of living nd none living organism
Chinaza
Biology is the study of life
Quadri
yes Sir
Said
what's cell biology
Prince
biology is the study of life
Raheal
what is asexual reproduction,?
Awoi Reply
A type of reproduction which does not involve the fusion of gametes or a change in the number of chromosomes
Serena
Reproduction without sex... In which form a single organism or cell makes a copy of itself.
Serena
Please explain the concept of mitosis and meiosis
Serena
I guess you could use it for study buddies and brushing up on what you need to
Serena
what is mitosis
Klp
Asexual reproduction?
Serena
why pepsin and trypsin released in active form?
Yacqub
mitosis is the type cell division in which two daughter cells have same no. of chormosomes
syed
Hi
Don
chromosome number remains the same in mitosis
mc
Ello
Henry
Hii
Nikky
Yrr help me.
Nikky
Physical chemistry..... Koi h jo mujhe physical chem ki notes send kr ske
Nikky
what is asexual reproduction
Targbe
what makes golgi body in plants
Abdulkareem Reply
name the membrane of the plants
Abdulkareem
how can turners syndrome be corrected before birth
Balinda
which animal survive from being preyed just because of being humble, slow, and not aggressive
Balinda
Plants have golgi body's also. Plants are eukaryotic cells. And membrane bound organelles are a characteristic of eukaryotic cells. Moreover golgi body's are creatted from the ER. Also do not forget plants have plastids and animal cells do not.
Eric
During organs transplantation, the organs cannot be taken from just anybody since the graft would be rejected sooner or later due to
Liter Reply
Non-MHC compatibility on the organ and an attack from the patient's immune system.
Eric
what makes golgi body in plants
Abdulkareem
why trypsin and pepsin released in active form
Yacqub
Let us remember MHC'S on our cells. This is how our cells determine self from n o n s e l f. Transplanted tissue has to have a certain amount markers. These have to match to the recipiant's markers. Even with this, immunosuppresant medacine is prescribed to the recipient.
Eric
Even with these measures the body may still reject the transport. This can occur even after the recipient excepting the transport for some time.
Eric
what is integument system
Joy Reply
This system is our skin. This includes the skin lining our alimentary system which includes the tissue from our mouth to our anus. Our skin is our largest organ system. It is mostly made up of epithelial tissue.
Eric
Cellular respiration
Lucy Reply
This is how our cells make energy. They use glucose + oxygen. There are other facors involves also. But these are the main two reactant used, for aerobic respiration. The main product is ATP. ATP is a high energy molecule which is paramount for life.
Eric
what are the characteristics of living things
Ruth Reply
Movement Respiration Nutrition/Feeding Irritability/Sensitivity Growth Excretion Reproduction Deat/Life span
Hashim
What makes children from the same father and mother sometimes don't look alike?
Hashim
One of the main one's is the abilit reproduce. That is why viruses are not considered living. Because they do not have the ability to replicate on they own.
Eric
identification of problems
Nana Reply
what happens in the process of raising the human arms
Nana
what is biology
Brandi Reply
first step in scientific method
Brandi
The study of living things.
Eric
In an investigation the pancreatic duct of a mammal was blocked.It was found that the blood sugar regulation remained normal while food digestion was impaired.Explain
Mac Reply
To begin with, obstruction of pancreatic duct will alter the blood sugar level as the juices responsible for glucose regulation will be rendered inconsequential. This will in turn affect the rate of digestion and absorbtion of digested food substances by the Villus .
Muktar

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Source:  OpenStax, Concepts of biology. OpenStax CNX. Feb 29, 2016 Download for free at http://cnx.org/content/col11487/1.9
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