White 6 "Cancer 1" Flashcards
define cancer
a disease in which an individual mutant clone of cells begin by prospering at the expense of its neighbor cells
What are the properties of cancer cells?
- cells are growing out of control
- become self sustaining, do not need signals to grow
- release autocrine growth factor
- cancer cells ignore apoptosis signals
- self-sufficient
- defective in cell cycle control mechanisms to stop the cell cycle
- gets help from stroll cells
- indices angiogenesis
- no replicative senescence
What are the basic differences between cancer cells and normal cells?
Cancer cells require little growth factors
normal cells have a strong requirement for growth factors
cancer cells become independent of stimulation that is normally required by cells the proliferate (decontrolled proliferation)
What are the two heritable properties of cancer cells
- reproduce in defiance of normal restraints on cell division and cell growth
- invade areas that are normally reserved for other cells
Describe how a tumor kills
it squeezes and destroys blood vessels and nerves until an organ stops functioning normally
Describe benign tumors
the neoplastic cells do not become invasive; is not cancer
Describe the 3 classifications of cancer
- carcinomas
- sarcomas
- leukemias and lymphomas
- carcinomas are from epithelial cells
- sarcomas are from connective and muscle tissues
- leukemias and lymphomas are from white blood cells and their precursors
Describe metastases
characteristic of cancer
invasive property
cancer cells break loose and enter into the blood or lymph and travel to new areas and form secondary tumors
THIS KILLS
Describe the development of cancer
- multiple mutational events
- all tumors are from a single ancestor
- mutations lead to a proliferative advantage and allow cells to grow rapidly
- develop slowly
Describe the development of colon cancer
- mutation in the APC gene in certain cells which have an advantage in cell growth
- polyps form which are technically benign tumors
- mutation in the Ras gene
- loss of tumor suppressor
- tumor moves into the blood stream
- gains capacity to invade
- NOW malignant
What is evidence that cancers are derived from a single cell?
- philadelphia chromosome (translocation between chi 9 and 22)
- smaller chromosome
- responsible for myelogenous leukemia
- comes from a single cell
What are the two types of carcinogens?
chemical and radiation
What are the two things that cancerous growth depends on?
defective apoptosis or defective growth
Describe the steps in the process of metastasis
- cells grow as a benign tumor in the epithelium
- cells become invasive and enter the capillary
- cells adhere to the blood vessel in the liver
- cells escape from the blood vessel to form micrometastasis
- colonize liver forming full blown mets
Describe angiogenesis
formation of new blood vessels
- tumors must get oxygen and nutrients like normal cells
- release factor to induce new blood vessel formation
- come from pre-existing blood vessel
Define neovascularization
formation of new blood vessels from scratch
What is the biggest environmental cause of cancer
tobacco
90% of people with lung cancer smoked
What are the two genetic causes of cancer
- tumor suppressor genes
2. oncogenes
What are the two types of broad mutations that regulate cell proliferation?
- overactivity mutations: gain of function of the oncogenes- single mutation event and activation of a gene causing proliferation
- under activity mutations: loss of function in the tumor suppressor genes that inhibit growth
Describe the differences between oncogenes and tumor suppressor genes
oncogenes are the gas pedal (gain of function) and the tumor suppressor genes (loss of function) are the brakes
oncogenes- one mutation leads to a dominant effect
tumor supressors- both copies must be mutated as it is recessive
Describe DNA maintenance genes
- subset of tumor suppressor genes
- mutations involve inactivation of the caretaker genes that create stability
- include DNA repair genes
Describe retroviruses and their relation to cancer and oncogenes
contain an RNA genome that can be transformed into DNA and integrated into the host
- transformed cells are small colonies of proliferative cells that are caused by oncogenes
- hijack proto-oncogenes and activate them via over-expression or cause mutations
Describe Ras
- first human oncogene
- monomeric GTPase for signal transduction
What are Ras oncogenes?
cannot shut off by hydrolyzing GTP to GDP
What are the 4 mutations that lead to the activation of proto-oncogenes into oncogenes
only one allele needs to be present for the activity to occur
- deletion or point mutation in the coding sequence
- regulatory mutation
- gene amplification
- chromosome rearrangment
Describe deletion or a point mutation in the activation of an oncogene
deletion or mutation in the coding sequence which makes a hyperactive protein
Describe the regulatory mutation in the activation of an oncogene
produce more than a normal protein which leads to a promoter mutation
Describe gene amplification in the activation of an oncogene
several copies of a normal protein are produced instead of one copy
Describe chromosomal rearrangement in the activation of an oncogene
beings new regulatory sequence that causes the overproduction or creates overactive fusion protein
Describe ligands and their relationship to cancerous cells
if produced consitutively, can cause proliferation and growth all the time; cancer cells can produce their own autocrine signaling
Describe the receptors and their relationship to cancerous cells
tyrosine kinase receptors- when RTKs constitutively produced do not need a ligand
Describe the transcription factor and their relationship to the cancerous cells
These proteins constantly induce transcription
- fos and jun activate gene expression including those important for cell cycle progression
- overproduction can lead to these to act as oncogenes
Define cell cycle proteins
anything that can cause cell proliferation; overproduction leads to cancer
What does Bcl2 do?
promotes cell survival despite DNA damage
-rearrangement mutation
via translocation this places Bcl2 under a new enhancer that induces a greater expression
-ACTIVE in B cells
