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
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
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
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
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