Chapter 20: Cancer Overview Flashcards
cancer results from the breakdown of
normal regulatory mechanisms that govern the cell
in cancer what results from accumulated abnormalities in multiple cell regulatory systems?
loss of growth control
define tumor
any abnormal pproliferation of cells
characteristics of a benign tumor
- remains confined to original location
- no invading/ spreading to distant body sites
characteristics of a malignant tumor
- capable of invading healthy tissue
- capable of metastasis
what are the 3 basic types of cancer?
- carcinomas
- sarcomas
- leukemias/lymphomas
carcinomas are malignancies of
epithelial cells
sarcomas are solid tumors of
connective tissues
muslce, bone, cartilage, fibrous tissue
tumors are further classified according to
- tissue of origin
- type of cell involved
provide 2 examples of cancers that describe the type of cells involved
- fibrosarcomas: fibroblasts
- erythroid leukemias: precursors of RBCs
most cancers develop late in life…why?
- cells become malignant
- mutations accumulate over time
normal tissue is a composite of cells in which different X chromosomes have been
inactivated
as normal tissue cells proliferate each displays the same patterm of X activation…what is it?
- X1: inactive
- X2: active
tumors begin to develop from a
single initially altered cell
what are the 4 types of growth patterns?
- hypertrophy
- hyperplasia
- dysplasia
- neoplasia
characterists of hypertrophy
- increase cell size
- normal organization
characteristics of hyperplasia
- increase cell #
- normal organization
characteristics of dysplasia
disorganized growth
characteristics of neoplasia
- disorganized growth
- net increase in dividing cells
what are the 3 stages of carcinogenesis?
- initiation
- promotion
- progression
the initiation stage of carcinogenesis constitutes…
a mutation
as a tumor progresses it increases its
growth rate & malignancy
what is an examples of tumor progression?
colon carcinoma
the proliferation of colon epithelial cells give rise to a small benign
adenoma/polyp
colon selection leads to
- adenoma growth
- increase size
- increase proliferative potential
malignant carcinoma
what are the 8 characteristics of cancer?
- density-dependent inhibition
- reduced dependence on GFs
- abnormal/blocked differentiation
- reduced cell adhesion
- angiogenesis
- protease secretion & metastasis
- resistance to apoptosis
- capacity for unlimited replication
describe density-dependednt inhibition
- normal cells multiply until they reach an optimal density
- tumor cells continue to proliferate uncontrollably
normal fibroblast cell migration is self-limited by
cell contact
tumor cells are not inhibited by cell contact
in leukemic cells differentiation is blocked at a stage where they still have the ability to
continue proliferating
what facilitated metastasis?
reduced cell adhesion
malignant cells secrete proteases that digest
extracellular matix components allowing invasion into connective tissue, blood vessels, lymphatic ducts
resistance to apoptosis is often caused by a
pathway mutation
the capacity for unlimited replication is a result of
telomerase expression
focus assay takes advantage if what 3 properties of transformed cells?
- altered morphology
- loss of contact inhibition
- loss of density-dependent inhibition
list some examples of carcinogens
- UV radiation
- chemical toxins
- mutagens
- tumor promoters
- viruses
UV radiation is likely to cause
skin cancer
list 4 examples of chemical toxins
- tobacco
- asbestos
- benzenes
- aflatoxin
mutagens damage
DNA
list examples of tumor promoters
- phorbol esters
- endocrine disruptors
- hormones
what are the steps of tumor viruses in permissive cells
virus replication
cell lysis
release of virus particles
what are the steps of tumor viruses in non-permissive cells
virus replication
some cells are permanently transformed
80% of human cancers are NOT induced by
viruses
what is considered the prototype of a highly oncogenic retrovirus
RSV
studies of RSV lead to the
identification of the first viral oncogene
what are the 4 things found in RSV genones?
- virion structural proteins
- reverse transcriptase integrase
- envelope glycoproteins
- Src tyrosone kinase
what are the 3 genetic sources of cancer?
- oncogenes
- tumor suppresor genes
- DNA repair genes
what are known as the accelorators in cancer
oncogenes
what are known as the brakes in cancer?
tumor suppresor genes
what are known as the mechanics of cancer?
DNA repair genes
oncogenes are normally
growth promoting
oncogenes as a normal gene is called
proto-oncogene
oncogenes when mutated induce
transformation
oncogenes can be
viral or cellular
tumor suppressor genes when mutated can NOT arrest
proliferation
Rb, p53
human oncogenes are usually homologous of
viral counterparts
oncogenes result from
- single point mutations
- chromosomal translocations
genes of regulatory mechanisms Ras
DNA extracted from human bladder carcinoma induced the
transformation of transfected mouse cells in culture
Ras mutants cannot carry out
GTP hydrolysis
results in constitutively active protein
what is the single point mutation of Ras
Gly is substituted for Val
oncogenes proteins act as
- GFs (EGF)
- GF receptors (ErbB)
- intracellular signaling molecules (Ras/Raf)
Ras/Raf oncogenes constitutively activate the
ERK MAP kinase pathway
describe the translocation of c-myc
proto-oncogene is translocated from C8 to the IgH on C14
the translocation of c-myc results in
Burkitt’s lymphoma
malignancy of antibody producing B cells
Tel/PDGF oncogene encodes a fusion protein where the extra-cellular domain of the normal receptor is replaced by the
Tel transcription factor
in Tel/PDGF oncogene activation the helix-loop-helix induces
dimerization of PDGFr & continuous activation of the protein kinase
what is the prototype of a tumor suppressor gene
Rb
tumor suppressor genes target
cyclin D/Cdk4,6
tumor suppresor genes where first identified as the product of a gene responsible for
retinoblastoma
unphosphorylated Rb binds to the
E2F transcription factor
Rb binding to the E2F transcription factor prevents
- transcription of genes for DNA replication
- passage through the G1 checkpoint into S phase
phosphorylated Rb cannot bind
E2F
E2F then activates
gene transcription triggering the onset of S phase
when retinoblastoma is hereditary the 1st mutation is already present in the
germ line
when retinoblastoma is nonhereditary the 1st mutation is present after the
first somatic division
what are characteristics of retinoblastoma?
- thickening of optic nerve
- displaced retina
