Ch 7: Neoplasm Flashcards
define neoplasm
new, abnormal proliferation of cells
can be benign or malignant
what two cell types are neoplasms made of
neoplastic cells (parenchyma of tumor)
nonneoplastic stroma (CT, blood vessels, and inflammatory cells)
what is differentiation
extend to which the neoplastic parenchymal cells resemble normal parenchymal cells
what is well-differentiated
neoplastic parenchymal cells that similarly resemble the other parenchymal cells in the area
characteristic of benign tumors
what is poorly-differentiated
neoplastic parenchymal cells do not resemble other parenchymal cells in the area
characteristic of malignant tumors
define anaplasia
cells that lose their organization and differentiation
poorly differentiated
what is a sarcoma
malignant tumor of mesenchymal origin
what is a carcinoma
malignant tumor of epithelial origin
what are the two main phases of the normal cell cycle
interphase (90% of cycle) and M phase (10% of cycle)
what are the two components of the M phase
mitosis and cytokinesis
what is mitosis
nuclear division
what is cytokinesis
division of everything in the cell except for the nucleus
what happens during interphase
cell is growing and preparing for division
split into: G1, S, and G2 phases
what is happening during G1 of the interphase
M phase or quiescent (stable/dormant) cells are entering
lots of proteins being made
cells are performing normal, daily metabolic activities and growing
what happens during the S phase
labile cells entering
DNA is replicating
what happens during G2 (gap 2) phase
producing more proteins and centrioles
what is an example of a quiescent (stable/dormant) cell
hepatocytes
what are 2 examples of permanent cells
neurons and cardiac myocytes
what are two examples of labile cells
epidermis and GI epithelium
what are the 5 steps in the cell cycle
G1 phase
S phase
G2 phase
M phase
cytokinesis
“Go Sally Go, Make Children”
what is the first checkpoint of the cell cycle
between G1 and S phases
checks for DNA damage
prevent damaged DNA from being made
p53 dependent
what is the second checkpoint of the cell cycle
between G2 and M phases
checks for damaged or unduplicated DNA
prevents chromosomal abnormalities
p53 independent/dependent
what are the three things that help to regulate the cell cycle
cyclin dependent kinases (CDK)
cyclins
cell cycle inhibitors
what are cyclin dependent kinases (CDK)
kinases which drive the cell cycle
available all the time in inactive forms
what are cyclins
molecules (B, E, A, and D) used to activate cyclin dependent kinases (CDK) at different points during the cell cycle
only made during certain cycles and then broken down
what do cell cycle inhibitors do
enforce the cell cycle checkpoints
explain how a growth factor can lead to cell growth
growth factor binds to membrane protein
binding activates inactive signal transduction pathway (RAS, MAPK, MYC)
active RAS activates other things which leads to production of D cyclins
cyclin D binds with CDK4 to make a complex
leads to something like Retinoblastoma (Rb) being phosphorylated
phosphorylation leads to E2F transcription factor being released
cyclin E binds to CDK2 to make a complex
complex leads to DNA replication
what are the two families of cell-cycle inhibitors
CIP/KIP and INK4/ARF
what are the three types of CIP/KIP cell-cycle inhibitors and what do they do
p21, p27, and p57
inhibit cyclins from binding to CDK
what are the two types of INK4/ARF cell-cycle inhibitors and what do they each do
p16 (INK4) - competes with CDK4 for binding to cyclin D
p14 (ARK) - prevents p53 degradation by inhibiting MDM2 activity
what is a proto-oncogene
normal genes within your body that promote cell proliferation
what is an oncogene
mutated or over expressed version of proto-oncogene that cause excessive cell growth
considered dominant
what is a tumor suppressor gene
genes that stop cell proliferation
recessive - two mutations to change the function
ex. TP53
what is an oncoprotein
protein encoded by oncogene
oncogene will increase or alter function of oncoprotein to increase cell proliferation
what are the 5 types of oncoproteins
GFR
RAS
PI3K
MYC
D cyclin
what are three ways in which an oncogene can become activated
gene amplification
point mutation
chromosome rearrangement (translocation)
what is the PDGFB gene
platelet derived growth factor beta
important growth factor involved in certain cancers like glioblastomas
what are the two main types of growth factor receptor genes
ERBB2 (HER) and PDGFRP
what is paracrine stimulation
growth factor stimulates itself and neighboring cells
what is autocrine stimulation
cell releases growth factor which binds to its own receptors
which two proteins involved in signaling transduction can be mutated to become oncogenes
ABL and RAS
what is a Philadelphia chromosome
translocation of ABL into BCR gene
fusion of these genes leads to over activation of tyrosine kinase and therefore growth factor signaling pathways
what is MYC
a nuclear regulatory protein that can be mutated to become an oncogene
mutation in this leads to Burkitt lymphoma
what is CCND1 (cyclin D1)
a cell cycle regulator that helps to activate cyclin dependent kinases
can become an oncogene once mutated
a mutation in the PDGFB leads to which type of cancer
astrocytoma
what controls cell-cycle checkpoints
tumor supressor proteins
ex. RB and p53
what is retinoblastoma
malignant tumor of the retina caused by mutations in 2 normal Rb gene
two forms: sporadic and familial
what is the familial form of retinoblastoma
40% of cases
child inherits one defective Rb gene
another Rb gene undergoes spontaneous mutations
what is the sporadic form of retinoblastoma
60%
two Rb mutations in somatic cells (not inherited)
what is a negative regulator of G1/S cell cycle
RB gene and Rb protein
what do the BRCA1 and 2 genes do
repair double-stranded breaks in DNA
what is the normal function of the RB gene and Rb protein and what happens when it goes array
stops cell progression from G1 phase to S phase until they’re ready to divide
mutations in this gene/protein can lead to DNA damaged cells dividing which can lead to glioblastoma
what does the neurofibromin-1 (NF1) gene do
tumor supressor gene that inhibits RAS/MAPK signaling
what does the TP53 gene and p53 protein do
stop cell cycle during G1 and cause DNA repair or apoptosis of a damaged cell
what is p53
guardian of the genome protein
activated by anoxia, inappropriate signaling, or DNA damage
regulates cell cycle arrest (G1), DNA repair, cellular senescence, and apoptosis
how does p53 control cell cycle arrest during G1
induce transcription of p21 which is a cell-cycle inhibitor
how does p53 repair DNA damage
using GADD45 protein
how does p53 cause apoptosis
promotes BAX
how is p53 regulated
by MDM2 enzyme
degrades p53 once it’s no longer needed
what is cellular senescence
stops cell from dividing and shuts it down
down by p53
what is TP53’s 2 main roles in causing cancer
germline mutation in a TP53 allele
or
p53 inactivation by viral oncoprotein which causes it to act like a MDM2, p53 is degraded (HPV)
what is the Warburg effect
tumor cells undergo a metabolic switch to aerobic glycolysis
increase uptake of glucose which converted to lactate
produces 2ATP and metabolic intermediates
why do cancer cells practice the Warburg effect instead of using oxidative phosphorylation
lactate and metabolite products are more efficient for lipid and molecular building block production
what are the two mechanisms of how cancer cells resist apoptosis
intrinsic (mitochondrial) pathway is affected
loss of TP53 function or complication of MDM2
prevents up regulation of PUMA
or
over expression of anti-apoptotic members of the BCL2 family
what is PUMA
pro-apoptotic protein
what are the two ways cancer cells practice immortality
cancer cells can restore telomeres to continue division by using telomerase
they can also inactivate senescence signals (signals that tell them to stop dividing)
how do cancer cells practice angiogenesis
increase angiogenic factors or loss of angiogenic inhibitors
how does hypoxia trigger angiogenesis
transcription factors release cytokines like VEGF and bFGF
leads to proliferation of endothelial cells and new growth of vessels
how do proteases affect angiogenesis
influence balance angiogenic and antiangiogenic factors
what is meant by neoplastic progression
cancers pick up different mutations along the way as they grow
for example, they start off with just angiogenic properties then pick up metastatic and non antigenic properties
what are the three ways in which cancer can spread to other areas of the body
direct seeding
lymphatic spread
hematogenous spread
what is hematogenous spread of tumor
cells detach from the tumor
go through and degrade the extra-cellular membrane
access capillaries to migrate to distant site
how do cancer cells survive as they’re traveling through the blood
bind to platelets to protect them
what is direct seeding and which cancers use this method most
metastasis method where cancer cells penetrates into a neutral open field
seen in ovarian carcinomas that spread to peritoneal surfaces
what are the 3 most common sites of metastasis of the colon/pancreas/stomach
liver, lung, and nodes
what are the 5 most common sites of metastasis of the breast
nodes, lung, bone, liver, and chest wall
what are the 4 most common sites of metastasis of the lung
brain, liver, nodes, and bone
what is the most common site of metastasis of the prostate
bone
what are the 3 most common sites of metastasis of melanoma
liver, brain, and lung
what are the three ways in which tumor cells can evade host immune response
loosing expression of antigens
loosing expression of MHC molecules
producing immunosuppressive cytokines or ligands
how does UV light cause cancer
causes two thymine bases to bind by covalent bonds (thymine dimers)
typically rare because your body eliminates these cells
what is the repair mechanism for X-ray, oxygen radical, alkylating agent, and spontaneous reaction damage
base-excision repair (BER)
what is the repair mechanism for UV light and polycylcic aromatic hydrocarbon damage
nucleotide-excision repair (NER)
what is the repair mechanism for X-ray and anti-tumor agent damage
recombinational repair (HR, EJ)
what is the repair mechanism for replication errors
mismatch repair
what is the nucleotide excision repair pathway
enzyme repairs DNA damage where several genes are involved
mutation in this pathway can lead to xeroderma pigmentosum (skin cancer)
what is epigenetic modification
changing the expression of genes without changing DNA sequences
three ways: DNA methylation, nucleosome remodeling, and histone modifications
all lead to gene silencing
can be passed down
what is DNA methylation
a method of epigenetic modification
methylation group is added which prevents transcription by shutting off gene expression of whole segments
takes two hits to get silencing
where do you see the most methylation in cancers
promotor region of many tumor suppressor genes
do oncogenes use hyper or hypomethylation
hypomethylation
do tumor supressor genes use hyper or hypomethylation
hypermethylation
what is the relationship between transcription and methylation
the more methylation you have, the less transcription
