1. Viruses to Cancer
What is cancer?

2. Loss of Normal Growth Control
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Normal cell division
Cell Suicide or Apoptosis
Cell damage— no repair
Cancer cell division
Cancer arises from a loss of normal growth control. In normal tissues, the rates of new cell growth and old cell death are kept in balance. In cancer, this balance is disrupted. This disruption can result from uncontrolled cell growth or loss of a cell’s ability to undergo cell suicide by a process called“apoptosis.” Apoptosis, or “cell suicide,” is the mechanism by which old or damaged cells normally self-destruct.
First mutation
Second mutation
Third mutation
Fourth or later mutation
Uncontrolled growth
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3. Example of Normal Growth Understanding Cancer and Related Topics
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Understanding Cancer and Related Topics
Understanding Cancer
Dead cells shed from outer surface
Epidermis
Cell migration
Dividing cells in basal layer
Dermis
To illustrate what is meant by normal growth control, consider the skin. The thin outermost layer of normal skin, called the epidermis, is roughly a dozen cells thick. Cells in the bottom row of this layer, called the basal layer, divide just fast enough to replenish cells that are continually being shed from the surface of the skin. Each time one of these basal cells divides, it produces two cells. One remains in the basal layer and retains the capacity to divide. The other migrates out of the basal layer and loses the capacity to divide. The number of dividing cells in the basal layer, therefore, stays the same.
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4. The Beginning of Cancerous Growth
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Understanding Cancer
During the development of skin cancer, the normal balance between cell division and cell loss is disrupted. The basal cells now divide faster than is needed to replenish the cells being shed from the surface of the skin. Each time one of these basal cells divides, the two newly formed cells will often retain the capacity to divide, thereby leading to an increase in the total number of dividing cells.
Underlying tissue
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5. Understanding Cancer and Related Topics
Tumors (Neoplasms)
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Understanding Cancer and Related Topics
Understanding Cancer
This gradual increase in the number of dividing cells creates a growing mass of tissue called a “tumor” or “neoplasm.” If the rate of cell division is relatively rapid, and no “suicide” signals are in place to trigger cell death, the tumor will grow quickly in size; if the cells divide more slowly, tumor growth will be slower. But regardless of the growth rate, tumors ultimately increase in size because new cells are being produced in greater numbers than needed. As more and more of these dividing cells accumulate, the normal organization of the tissue gradually becomes disrupted.
Underlying tissue
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6. Invasion and Metastasis Understanding Cancer and Related Topics
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer 1
Cancer cells invade surrounding tissues and blood vessels 2
Cancer cells are transported by the circulatory system to distant sites
Cancers are capable of spreading throughout the body by two mechanisms: invasion and metastasis. Invasion refers to the direct migration and penetration by cancer cells into neighboring tissues. Metastasis refers to the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through the bloodstream, and then invade normal tissues elsewhere in the body. 3
Cancer cells reinvade and grow at new location
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7. Malignant versus Benign Tumors Understanding Cancer and Related Topics
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Understanding Cancer and Related Topics
Understanding Cancer
Benign (not cancer) tumor cells grow only locally and cannot spread by invasion or metastasis
Malignant (cancer) cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
Depending on whether or not they can spread by invasion and metastasis, tumors are classified as being either benign or malignant. Benign tumors are tumors that cannot spread by invasion or metastasis; hence, they only grow locally. Malignant tumors are tumors that are capable of spreading by invasion and metastasis. By definition, the term “cancer” applies only to malignant tumors.
Time
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8. Microscopic Appearance of Cancer Cells
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Understanding Cancer and Related Topics
Understanding Cancer
Cancer tissue has a distinctive appearance under the microscope. Among the traits the doctor looks for are a large number of irregularly shaped dividing cells, variation in nuclear size and shape, variation in cell size and shape, loss of specialized cell features, loss of normal tissue organization, and a poorly defined tumor boundary.
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9. Understanding Cancer and Related Topics
What Causes Cancer?
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Understanding Cancer and Related Topics
Understanding Cancer
Some viruses or bacteria
Some chemicals
Radiation
Heredity
Diet
Hormones
Cancer is often perceived as a disease that strikes for no apparent reason. While scientists don’t yet know all the reasons, many of the causes of cancer have already been identified. Besides intrinsic factors such as heredity, diet, and hormones, scientific studies point to key extrinsic factors that contribute to the cancer’s development: chemicals (e.g., smoking), radiation, and viruses or bacteria.
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10. Viruses Virus inserts and changes genes for cell growth
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Virus inserts and changes genes for cell growth
In addition to chemicals and radiation, a few viruses also can trigger the development of cancer. In general, viruses are small infectious agents that cannot reproduce on their own, but instead enter into living cells and cause the infected cell to produce more copies of the virus. Like cells, viruses store their genetic instructions in large molecules called nucleic acids. In the case of cancer viruses, some of the viral genetic information carried in these nucleic acids is inserted into the chromosomes of the infected cell, and this causes the cell to become malignant.
Cancer-linked virus
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11. Examples of Human Cancer Viruses
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Understanding Cancer and Related Topics
Understanding Cancer
Some Viruses Associated with Human Cancers
Only a few viruses that infect human cells actually cause cancer. Included in this category are viruses implicated in cervical cancer, liver cancer, and certain lymphomas, leukemias, and sarcomas. Susceptibility to these cancers can sometimes be spread from person to person by infectious viruses, although such events account for only a very small fraction of human cancers. For example, the risk of cervical cancer is increased in women with multiple sexual partners and is especially high in women who marry men whose previous wives had this disease. Transmission of the human papillomavirus (HPV) during sexual relations appears to be involved.
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12. Replication & Variety of DNA Viruses
SV40 Virion
HPV 16 Virion
Figure 3.3 The Biology of Cancer (© Garland Science 2007)

13. AIDS and Kaposi’s Sarcoma
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Without
disease
HIV infection
Depressed
immune
system
KSHV infection
Kaposi’s
sarcoma
People who develop AIDS after being infected with the human immunodeficiency virus (HIV) are at high risk for developing a specific type of cancer called Kaposi’s sarcoma. Kaposi’s sarcoma is a malignant tumor of blood vessels located in the skin. This type of cancer is not directly caused by HIV infection. Instead, HIV causes an immune deficiency that makes people more susceptible to viral infection. Infection by a virus called KSHV (Kaposi’s sarcoma- associated herpesvirus) then appears to stimulate the development of Kaposi’s sarcoma.
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14. Understanding Cancer and Related Topics
Genes and Cancer
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Viruses
Chemicals
Radiation
Heredity
Chemicals (e.g., from smoking), radiation, viruses, and heredity all contribute to the development of cancer by triggering changes in a cell’s genes. Chemicals and radiation act by damaging genes, viruses introduce their own genes into cells, and heredity passes on alterations in genes that make a person more susceptible to cancer. Genes are inherited instructions that reside within a person’s chromosomes. Each gene instructs a cell how to build a specific product--in most cases, a particular kind of protein. Genes are altered, or “mutated,” in various ways as part of the mechanism by which cancer arises.
Chromosomes are DNA molecules
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15. Proto-Oncogenes and Normal Cell Growth
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Normal Growth-Control Pathway
Growth factor
Receptor
Signaling enzymes
Transcription factors
DNA
Cell nucleus
Oncogenes are related to normal genes called proto-oncogenes that encode components of the cell’s normal growth-control pathway. Some of these components are growth factors, receptors, signaling enzymes, and transcription factors. Growth factors bind to receptors on the cell surface, which activate signaling enzymes inside the cell that, in turn, activate special proteins called transcription factors inside the cell’s nucleus. The activated transcription factors “turn on” the genes required for cell growth and proliferation.
Cell proliferation
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16. Oncogenes are Mutant Forms of Proto-Oncogenes
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Inactive growth factor receptor
Inactive intracellular signaling protein
Signaling protein from active oncogene
Activated gene regulatory protein
Transcription
Oncogenes arise from the mutation of proto-oncogenes. They resemble proto-oncogenes in that they code for the production of proteins involved in growth control. However, oncogenes code for an altered version (or excessive quantities) of these growth-control proteins, thereby disrupting a cell’s growth-signaling pathway.
By producing abnormal versions or quantities of cellular growth-control proteins, oncogenes cause a cell’s growth-signaling pathway to become hyperactive. To use a simple metaphor, the growth-control pathway is like the gas pedal of an automobile. The more active the pathway, the faster cells grow and divide. The presence of an oncogene is like having a gas pedal that is stuck to the floorboard, causing the cell to continually grow and divide. A cancer cell may contain one or more oncogenes, which means that one or more components in this pathway will be abnormal.
Cell proliferation driven by internal oncogene signaling
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17. Tumor Suppressor Genes
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Normal cell
Normal
genes
prevent
cancer
Remove or inactivate tumor suppressor genes
Cancer cell
Damage to
both genes
leads to
cancer
A second group of genes implicated in cancer are the “tumor suppressor genes.” Tumor suppressor genes are normal genes whose ABSENCE can lead to cancer. In other words, if a pair of tumor suppressor genes are either lost from a cell or inactivated by mutation, their functional absence might allow cancer to develop. Individuals who inherit an increased risk of developing cancer often are born with one defective copy of a tumor suppressor gene. Because genes come in pairs (one inherited from each parent), an inherited defect in one copy will not lead to cancer because the other normal copy is still functional. But if the second copy undergoes mutation, the person then may develop cancer because there no longer is any functional copy of the gene.
Mutated/inactivated
tumor suppressor genes
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18. Tumor Suppressor Genes Act Like a Brake Pedal
National Cancer Institute
Understanding Cancer and Related Topics
Understanding Cancer
Tumor Suppressor Gene Proteins
Growth factor
Receptor
Signaling
enzymes
Transcription factors
DNA
Cell nucleus
Tumor suppressor genes are a family of normal genes that instruct cells to produce proteins that restrain cell growth and division. Since tumor suppressor genes code for proteins that slow down cell growth and division, the loss of such proteins allows a cell to grow and divide in an uncontrolled fashion. Tumor suppressor genes are like the brake pedal of an automobile. The loss of a tumor suppressor gene function is like having a brake pedal that does not function properly, thereby allowing the cell to grow and divide continually.
Cell proliferation
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19. RNA Tumor Viruses – The Rous Sarcoma Virus Story
Figure 3.2 The Biology of Cancer (© Garland Science 2007)

20. Figure 3.22 The Biology of Cancer (© Garland Science 2007)

21. Viruses and Their Oncogenes
Virus Oncogene
Rous sarcoma virus v-src
Simian sarcoma virus v-sis
Avian erythroblastosis v-erbA/B
Kirsten murine sarcoma v-kRas
Moloney murine sarcoma v-mos
MC29 avian myelocytoma v-myc

22. Retroviral Insertion Has the Potential to Transform by Activation of Oncogenes
Figure 3.23b The Biology of Cancer (© Garland Science 2007)

23. Many Types of HPVs Different HPVs–Different Infections Harmless
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
Different HPVs–Different Infections
Harmless
No warts or cancer
Warts-Linked
Genital warts
Cancer-Linked
Most clear up
Some persist, but no abnormalities in cervix
Some persist, some abnormalities in cervix
A few persist and progress to cervical cancer
There are three groups of genital HPV strains: many no-risk types cause neither warts nor cancer; a few types cause genital warts; and 15 or so high-risk types can increase one’s risk of cancer.
If left untreated, genital warts do not turn into cancer.
High-risk HPV, on the other hand, may trigger an infection that leads to cervical cancer. The majority of infections with high-risk HPVs clear up on their own. Some infections persist without causing any additional abnormal cell changes. However, a few infections caused by high-risk HPVs end up triggering cervical cancer over many years.
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24. Common Infection Infected with HPV
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
Infected with HPV
Human papillomavirus (HPV) is the most common sexually transmitted virus in the United States. At least 70 percent of sexually active persons will be infected with genital HPV at some time in their lives. HPV infects both men and women.
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25. Virus Penetrates Cervix
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
Papillomavirus
Uterus
Layers of
epithelial cells
Cervix
HPV
infection
Both harmless and cancer-linked human papillomaviruses pass by skin-to-skin contact. The high-risk types of HPVs need to penetrate deeply into the lining of the cervix to establish a chronic infection. A vaginal sore or sex, which can abrade the lining, may provide a point of entry for the papillomavirus.
Once inside the cervical lining, the virus attaches to epithelial cells. As these cells take in nutrients and other molecules that are normally present in their environment, they also take in the virus. Over 99 percent of cervical cancer cases are linked to long-term infections with high- risk human papillomaviruses.
Vagina
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26. Virus Uncoats Nucleus Viral DNA enters nucleus
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
Nucleus
Viral DNA enters nucleus
mRNAs for viral proteins E6 and E7
Virus
“uncoats”
The HPV sits inside the epithelial cells housed in a protective shell made of a viral protein called L1. After the virus enters the cell, the viral coat is degraded, leading to the release of the virus’ genetic material into the cell and its nucleus. From the nucleus, the genes of the virus are expressed, including two genes called E6 and E7, which instruct the cell to build viral proteins called E6 and E7.
Epithelial cell interior
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27. Virus Disables Suppressors
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
Mucus
Healthy cells
E6 viral protein
Cancerous epithelial cells
Suppressor protein 1
Degraded suppressors
E7 viral protein
Suppressor protein 2
Viral proteins E6 and E7 then disable the normal activities of the woman’s own suppressor genes, which make suppressor proteins that do “damage surveillance” in normal cells. These proteins usually stop cell growth when a serious level of unrepaired genetic damage exists. Even after suppressors are disabled in a woman’s cervical cells, it usually takes more than 10 years before the affected tissue becomes cancerous.
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28. The Vaccination HPV Vaccine to Prevent Cervical Cancer
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
The vaccination protects a person from future infection by the HPV high-risk types that can lead to cancer. It is not a vaccine against cancer itself. A person receives a series of three shots over a 6-month period. Health professionals inject these virus-like particles into muscle tissue. Once inside, these particles trigger a strong immune response, so the vaccinated person’s body makes and stockpiles antibodies that can recognize and attack the L1 protein on the surface of HPV viruses.
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29. Antibodies Prevent Infection
National Cancer Institute
Understanding Cancer and Related Topics
HPV Vaccine to Prevent Cervical Cancer
Papillomavirus
After the vaccination, the person’s immune cells are prepared to fight off future infection by high-risk HPV viruses. If an exposure occurs, the vaccinated person’s antibodies against the L1 protein coat the virus and prevent it from releasing its genetic material.
No DNA strands can escape the capsid
= Antibodies
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