Cancer Genetics Exam One

Bio 477 JMU

6 hallmarks of a cancer cell

controlled cell proliferation, growth suppressing signals, control of cell movement, finite cell replication, limited angiogenesis, appropriate cell death

density dependent cell division inhibition

cell growth is limited by presence of surrounding cells in a monolayer; tumor cells have lost their ability to sense neighboring cells and just pile on top of each other.

what protein signals contact inhibition

HIPPO

substrate dependent contact inhibition

cancer cells grow well even when cells are suspended due to decreases in syndecans-4

extending the hayflick limit

increase in telomerase

cell cycle protein mutation

rb is always phosphorylated so E2F can stay active

heart of tumor development

control of DNA damage

BRCA-1

involved in DNA repair, one mutant allele in inherited breast cancer

hypertrophy

increase in cell size, normal organization

hyperplasia

increase in cell #, normal organization

dysplasia

disorganized growth

neoplasia

disorganized growth, increase in the number of dividing cells

tumors are ____ in nature meaning the mass originates from the same cell

monoclonal

characteristics of a benign tumor

local growth, slow growth, well differentiated, rarely terminal

characteristic of a malignant tumor

metastatic, slow or rapid, variable differentiation, often terminal

tumor angiogenesis

increase activators, reduce inhibitors to vascularize the cell leading to increase growth and invasion of the cell.

father of angiogenesis

judah folkman

iressa angiogenesis targeted drug

blocks production of VEGF

Avastin angiogenesis targeted drug

neutralizes VEGF

Sutent angiogenesis targeted drug

blocks receptors for VEGF and other angiogenesis stimulators

invasion

migration into local tissues

Metastasis

cancer entering through the bloodstream

p53

transcription factor that senses stress signals, DNA damage triggers activation and suppresses tumors

rb

tumor suppressor, cell cycle controller, transitions cell cycle through phosphorylation of the receptor allowing E2F to unbind

ETS/TCF

binding motif, catalytic subunit of telomerase

TWIST

controls gene expression, controls epithelial cells and their functionality

EMT

we want it during development but not after

control of cell death

mutations that repress apoptosis allow damaged cells to survive and evolve

syndecan 4 levels in colon cancer vs breast cancer

breast cancer is up, colon cancer is down

carcinoma

epithelial cells

sarcoma

supporting tissue

lymphoma 

lymph nodes-leukemia 

benign naming

oma

malignant naming

general type orgin

chemical carcinogenesis

chemical induced cancerous transformation of normal cells

benzo(a)pyrene

in cigarette smoke, metabolized in numerous tissues creating the reactive species that binds to guanine causing DNA distortion

Asbestos 

enters the lungs and penetrated into the chest cavity causing chronic inflammation 

What does asbestos inflammation lead to 

leads to the development of mesothelioma, inflammatory leukocytes cause oxidative stress, causing DNA adducts interfering with mitosis, stimulating proliferation. 

Aflatoxin

toxic chemicals produced by mold aspergillus, requires metabolic activation

what does aflatoxin do to the liver

promotes excessive necrosis leading to scarring and abnormal liver nodules. as they worsen p53 is lost and telomerase is activated in a hepatocellular carcinoma.

initiation of a hepatocellular carcinoma

introduction of a mutation by a carcinogen

promotion of a hepatocellular carcinoma

prolonged stimulation of proliferation in damaged cells 

progression of a hepatocellular carcinoma 

evolution and selection of more aggressive and invasive cells 

phorbol ester

mimics the binding properties of DAG, binding to protein kinase C, continually activating cell division

the AMES test

bruce ames, accounted for possible procarcinogenic nature of chemicals by expressing to liver enzymes

nucleotide excision repair

pyrimidine dimers repaired by activation of p53

Peyton Rous

transmitted sarcoma from affected chickens to healthy chickens by using filtered tumor extract

peter vogt and duesberg

perform focus forming assays with RSV

retrovral oncogenes

mutant forms of protooncogenes

viral oncogenes

evolved overtime to function without control during cell proliferation

Rous Sarcoma 

mutant version of tyrosine kinase src to turn on the cell 

viral src

lost regulatory phosphorylation site at amino acid 527, therefore it is always on

activated vsrc

promotes cell survival and proliferation

example of DNA virus that express oncoprotein that induce cell proliferation

HPV- E6 binds p53 preventing DNA repair, E7 binds to Rb preventing the association with E2F resulting in cell proliferation