Unit 3 - Viruses and Cancer Flashcards
What is Cancer?
Cancer: Uncontrolled growth of abnormal cells in the body
- 10^14 cells in the body; chance of individual cell becoming cancerous is ~3x10^-14
- Cancer can develop in almost any organ or tissue (more than 100 types of cancer)
- Cancer caused about 13% of all human deaths worldwide (7.9 million) in 2007
- rates are rising as more people live to an old age
- Three most common cancers in men: Prostate, lung, and colon
- Three most common cancers in women: Breast, colon and lung
What are the causes and risk factors in cancer?
Causes and Risk Factors:
- Carcinogens (asbestos)
- Behavior (alcohol use, smoking)
- Hormones (HRT)
- Psychological stress (?)
- Heredity
- Radiation and UV light
- Physical inactivity/obesity
- Viral infections (10-20% of cancers worldwide
What is the history of cancer viruses and tumors?
- Cancer has afflicted humans throughout history?
- Hipposcrates observed carcinomas (460-370B.C.)
- Percival Pott (1775): chimney sweeps and scrotal cancer caused by soot
- 18th century: 1st cancer hospital in Reims, France; cancer as contagious disease
What and Who was involved in Early cancer Research?
- Ellerman and Bang (1908): demonstrated that “filterable agents” (viruses) could produce tumors in chickens
- Peyton Rous (1911): demonstrated that a cell-free, bacteria-free filtrate could cause sarcomas (slow-growing solid tumors) in chickens
The transmissible agent was a retrovirus, later named Rous sarcoma virus (RSV)
1st identified oncogenic virus (“oncovirus”)
What is Bishop and Varmus?
- RSV genome: gag, pol, env, and src
- Discovered that the src gene is found in the normal DNA of chickens (and later mammals and humans).
- Their work demonstrated that oncogenes are cellular genes that were hijacked by viruses from cells.
- Cause cells to become transformed or cancerous
- 1989 Noble Prize
What is a viral oncogene (v-onc)?
It is a viral gene responsible fo roncogenicity of the virus
What is Proto-oncogene?
Proto-oncogene: cellular genes that promote normal growth and cell division
What is cellular oncogene?
Cellular oncogene: mutated form of proto-concogene that causes tumor formation
What are Tumor suppressor gene?
Tumor Suppressor gene: gene that inhibits conversion of normal cell into a cancer cell
What is Transformation?
Transforation: Change in the morphological, biochemical, or growth protperites of a cell
What is Metastasis?
Metastasis: when a cell or clump of cells separates from a tumor and spreads to another location.
How is the Eukaryotic Cell cycle and cancer involved in one another?
- Interphase (G1, S, G2)
- Mitosis
- Cytokinesis
- “Checkpoints” to monitor and regulate the cell cycle
- G1/S and G2/M
- Regulatory molecules
- Cyclins & cyclin-dependent kinases (CDKs)
- Dysregulation of cell cycle components may lead to tumor formation

What are Telomeres?
- DNA sequences found at the end of chromosomes
- Telomeres become shorter during normal aging
- Short telomere signals cell to stop dividing
- Telomerase: enzyme that synthesizes telomeric DNA (“TTAGGG“) on the ends of chromosomes
- Cancer cells contain increased levels of telomerase activity
- Telomere length never shortens and cell never stops dividing
What are the properties of Cancer or Transformed Cells In vitro (cell culture)?
- Genetic changes—polyploidy, high levels of telomerases
- Immortalization
- Metabolic changes—grow rapidly
- Lack of contact inhibition—cells pile up
- Anchorage independent—loss of adhesion
- Require less serum in medium to grow
- Loss of cell cycle control
- Changes in membrane structure and function
- Tumor-associated carbohydrate antigens
What is involved in properties in Cancer cells in vivo?
- Increased oncogene protein expression due to amplifications, translocations, or mutations
- Loss of tumor suppressor gene function due to deletion or mutation
- Cells divide uncontrollably
- Increased levels of enzymes important for nucleic acid synthesis
- Increased telomerase activity
- Malignant cells avoid host immunosurveillance
What the the different Assays to Detect Transformation?
- Focus-forming assay
- Soft agarose assay
- Reduced serum requirement
What is a Forcus Forming assay?
Focus-forming assay: transformed cells lose contact inhibition and grow on top of each other in dense piles (foci)
What is a Soft agarose assay?
Soft agarose assay: transformed cells can divide and form colonies when suspended in agarose
Wha tis reduced serum requirement?
Reduced serum requirement: transfomred cells can grow in media containing reduced serum (low 0.5% vs. normal 10%)
Since cancer is a Multistep process, what is involved in that multistep process?
- Cells bypass apoptosis
- Cells circumvent the need for growth signals
- Cells escape immunosurveillance
- Cells (tumors) command their own blood supply
- Cells may metastasize
- Tummor suppressor genes lose function
What are some of the viruses that are related to cancer?
- Viruses are associated with 10-20% of cancer worldwide
- At least six viruses are thought to contribute to cancers
- Hepatitis B virus
- Hepatitis C virus
- Human Papillomavirus
- Epstein-Barr virus
- Kaposi’s sarcoma-associated herpesvirus
- Human T-lymphotropic virus types 1 and 2 (HTLV-1 and -2)
What are the molecular mechanisms of virally-induced tumor formation by RNA tumor viruses?
Retrovirus genome
- pol encodes reverse transcriptase (RNA→DNA), integrase, Rnase H, and protease
- gag encodes matrix and core structure proteins
- env encodes “spike” proteins that are embedded in envelope and are critical for attachment
- Repetitive (R) and unique (U) sequences enable DNA copy of genome to be inserted into host DNA
Some retroviruses contain an additional gene (v-onc)
- not an essential gene
- hijacked from genome of host cells during evolution
- encodes a protein capable of inducing cellular transformation
What are the molecular mechanisms of how retroviruses can cause cancer?
Random integration of provirus into host cell DNA:
- Insertion within/near a cellular oncogene (c-onc)
- Insertional activation: abnormal expression of c-onc leads to uncontrolled growth
- Insertional inactivation of cellular tumor suppressor gene leading to uncontrolled cell division
- Integrated v-onc may become activated and transcribed
- Promoting normal cell growth and division; tumor formation
What are Human Retroviruses and how many have been identitfied?
Five human retroviruses have been identified:
- Human foamy virus
- HTLV-1
- Sexually transmitted (male → female)
- Most people infected are asymptomatic carriers
- 2-5% chance of developing Adult T-cell Leukemia (ATL)
- HTLV-2
* Hairy Cell Leukemia - HIV-1*
- HIV-2*