exam 3 - cancer 1 Flashcards
What are the characteristics of cancers cells?
- Two heirtable properties
- 1 .) Reproduce in defience of normal retriants on cell divisions and cell growth
- 2.) invade areas normally reserved for other cells
- Cancer cells (decontrolled proliferation)
- more selfsufficent
- dont need signals to grow
- grow via little autocrine growth factor signals
- ignore anti-growth signals and apoptosis signals
- defective in cell cycle control mechanisms
- dont need signals to grow
- gets help form stromal cells
- induces angiogenesis
- invasive to other tissues
- Does NOT show Replicative sensece (stops dividing after a # of divisons ) but ARE IMMORTAL
- more selfsufficent
How do benig tumors relate to malignate tumors
- Tumors
- when an abnormal cell grows and proliferates out of control and fibes rise to a neoplastic growth called a tumor
- Benign Tumors
- When a tumor has not become invasive and can be surgically removed
- Benign tumor presence DOES NOT mean cancer
- Malignant tumors
- Tumor is considered cancer when it is malignant (if cells have the ability to invade surround tissues
WHat is Metastases ?
- Invasiveness of cancer
- cancer cells can break loose, enter into blood orlymph , travel to new areas and formed secondary tumors
- Cant be eradicated by surgery or irradiation
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how do tumors develope?
- Involves multiple mutational events
- all tumors from single ancestor
- confer a proliferative advantage
- mutations allow cells to grow more rapidly than normal
- Tumors evolve form benign growth o invasive cancers and ultimately metastatic
- represents tumor progression
How does tumor development occur in colon cancer?
- cells with APC mutation gain advantage in growth
- Tumor suppressor
- form polyps
- at this point still benign
- Mutation in RAS which becomes a cancer gene
- Loss of other tumor suppressor - lose p53
- carcinoma (epithelial cells)
- Rumor moves out into blood stream
- gains capacity to invade
- becomes malignant tumor
What is the Philadelphia Chromosome?
- It is mutation that results form the translocation between Chr 9 + 22
- Responsible for chronic myeogenous leukemia
- all cancers cells have the same chromosomal aberration
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What are the causes of cancers?
- Carcinogenesis is linked to mutagenesis (mutant change of DNA)
- two types carcinogens: Chemical carcinogens and radiation (xrays, UV)
- carcinogens can be detected via ames test and look for bacteria dependent histadine growth
- Tobacco is most important environmental factor to cause cancer
- Virsus and infections are linked to cancer
- AIDS: HIV - human immunodeficiency virus causes kaposi sarcoma
- Ulcers and Helicobacter pylori can cause stomach cancer
- Virus that hijacks c-src ( gene for cellgrowth and prloferation) will cause over expression froma storng viral promoter or cause protooncogene into an oncogene
- Can be cause by either increased in cell divison or a decrease in apoptois
- a loss of programmed cell death or DNA repair causes a build up of mutations then leads to cancer
- Diets high fat/low fiber: accounts for 37% of bowel,pacreas, prostate, and breast cancer
How does tumor progression occur in the cervix?
- cervical cancer occurs in the cervix which is made out of stratified epithelia
- cell proliferation begins in basal epithelia
- Low grade and high grade intraepithelial neoplasia
- Can be removed at this stage
- It can develope into a cacinoma when the cells move through basal lamina and invade surrounding tissues and can enter blood
- BEst weapon we have agains cancer is early detection
- in this case a pap smear (scaping cells off of cervix)
What is the difference between Angiogenesis and Neovascularization?
- Angiogensis
- is the formtion of new blood vessels that are sprouted from old vessels
- tumors mmust get oxygen and nutrients like normal cells
- relase factor to induce new blood vessel formation
- is the formtion of new blood vessels that are sprouted from old vessels
- NEovascularization
- is the formation of new blood vesels basically from scratch or on the spot
What are Oncogenes
- Overactivity mutation that causes a gain in function = ONCOGENES
- onvolves a snigle mutation event and activation of gene proliferation (dominant)
Remember ONCO genes = GAIN of FUNCTION
A single copy of a mutation in the proto-oncogene converts and has a dominant effect
What are Tumor Supressor Genes?
- Underativity mutations: Loss of function - tumor repressor genes involve genes that inhibit growth. Mutation event: one gene - no effect ; second mutation causes probelms (recessive)
TUMOR REPRESSORS GENES = LOSS OF FUNCTION
What is the difference between oncogenes and tumor repressor genes?
- Oncogenes
- overactivity mutations
- gain of function
- invovles single mutation event and activation of gene causing proliferation
- Tumor Supression genes
- underactivity mutations
- loss of function
- involves geens that inhibit growth
- mutattionevnet
- one gene = no affect
- two genes = 2 affects
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How do mutations in DNA maintenance genes work?
- Subset of tumor supressors genes
- mutations invovle inactivation of caretaker genes that create geneomic stability
- include DNA repair genes, Checkpoint genes
What are two ways inwhich protoonco genes are converted into oncogenes?
- Deletion or point mutation in coding sequence
- hyperactive protein made in normal amounts
- Regulatory mutation (promotor mutation)
- normal protein greatly overproduced
- gene amplification
- normal protein greatly overprodice
- ( several copies instead on 1 )
- normal protein greatly overprodice
- chromsome rearrangement
- Nearby regulatory DNA sequences cayses normal protein to be overproduced
- Fusion to actively transcribed gene produces hyperactive fusion protein
Fun fact: first oncogene found was RAS. Ras is monomeric GTPase for signal transduction. Ras oncogenes cant shut off by hydrolyzing GTP and GDP
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What are the cellular functions of oncogenes (essential other situations that it causing cancer)
- Ligands:
- If ligands produced constitutively they cause proliferation and grow all the time (cancer cells produce own ligand autocrone signaling)
- Receptors:
- Tyrosine Kinase receptors - when RTKs constitutively produced dont even need a ligand
- transcription factors :
- in nucles, these proteins constantly induce trasncription
- activatie gene expression including those important for cell cycle progression - over production can lead these to act as oncogenes
- cell cycle proteins
- anything that can cause cell proliferation - overproduction of these leads to cancer
- Proteins that inhibit apoptosis
- Promotes cell survival despite DNA damage
- overproduction allow cancerous cells to survive and grow
- Ex: Bcl2
What is the Bcl2 oncogene?
- Results in over expression Bcl2 in B cells
- Instead of expression of AB, makes lots of Bcl2
- So prevents apoptosis of damaged cells - get DNA damage and cell proliferation and development of B cell lymphoma