Bio 235 Exam 3 Cancer
tumor suppressor proteins, encoded by tumor suppressor genes:
-loss or inactivation of just one can lead to cancer -few dozen proteins in entire proteome -fusion of normal cells to cancer cell yields hybrid that usually does not show cancer
_____ causes _____ cancer, but not if injected into the _____ directly, has to be acted upon by body's metabolism first
2-napthylamine, bladder, bladder
more than ___ human ______ identified
200, oncogenes
HeLa cells
20K divisions, derived from uterine cervical cancer
Hayflick limit
50-60 cell divisions
about _____ of cancer deaths due to dangerous spreading, rather than the growth of _____ _____
90%, primary tumor
Fibroblast Growth Factor (FGF)
A peptide growth factor, originally defined by its mitogenic effects on fibroblasts; also acts as an inducer during early brain development.
_____ _____ shows mutagenic potential of chemicals using microbes, chemicals may bind DNA directly. Necessary to react chemical with ____ _____ in ____ _____
Ames test, liver extract, Ames test
CHO
Chinese hamster ovary
cancer cells are unresponsive to_____
DNA damage as normal cells are
___ ______ can cause cancer, such as forming wrong bonds between bases, bonds being broken, bases removed, etc
DNA modification
cancer cells downregulate proteins like _____ _____ that is needed to keep cells _____ to each other
E-cadherin, attach
Burkitt's lymphoma
Epstein-Barr virus
Retinoblastoma controls cell cycle progression from __ to _ (at restriction point), important in many cancers
G1, S
___ produces __ protein, targets _____
HPV, E7, retinoblastoma
___ causes cancer (___ 16, 18, others), ___ vaccine prevents cancer, ___ 18 found inserted into genome of ___ cells
HPV, HPV, HPV, HeLa
Telomeres
Repeated DNA sequences at the ends of eukaryotic chromosomes.
insertional mutagenesis
Retroviruses integrate at random locations in the genome. Retroviral insertion can disrupt gene function or proper regulation of nearby genes.
What did Peyton Rous discover?
Rouse Sarcoma virus, caused cancer in chickens, this is an oncovirus (Nobel Prize over 50 years later)
some normal cells inhibit cancer cells by secreting _____ (controls proliferation through cell cycle and apoptosis). Some cancers are not resistant to this. Some cancer cells produce _____ themselves to inhibit growth of normal cells
TGFB, TGFB
"seed and soil" hypothesis
The metastases can only form in compatible microenvironments. This is why some cancers tend to lead to classic metastases.
ionizing radiation
X ray, radioisotopes (Chernobyl, radium, radon, etc), UV light
E-cadherin
a cell adhesion molecule that is expressed in normal breast tissue
what is portal vein?
a vein conveying blood to the liver from the spleen, stomach, pancreas, and intestines.
tumor cells show
anchorage-independent growth
some tumors downregulate compounds such as _____ that restricts vessel growth, showing another mechanism tumors evolved to support their growth
angiostatin
BHK 21
baby hamster kidney
prostate cancer often metastasizes to _____ because _____ cells produce molecular factors stimulating prostate cell growth, irrespective of _____ _____ _____
bone, bone, blood flow patterns
if both cells resulting from split retain ability to divide, then _______ can result
cancer
malignant
cancerous
"_____ _____" is making compound more likely to cause cancer following chemical modification
carcinogen activation
_____ causes cancer, but ______ must be acted upon by action of liver to cause cancer
carcinogens, procarcinogens
Autophagy
cell breaks down and destroys old, damaged, or abnormal proteins in cytoplasm
disruptions in _____ _____, pay attention to _____ _____
cell cycle, restriction site
hybridoma
cells formed via fusion between a short-lived antibody-producing B cell and an immortal myeloma cell
upregulation of cells response to _____ leads to _____ mobility of _____ cancer cells
chemoattractant, increase, metastatic
initiation
conversion of normal to precancerous cell such as coal tar components, permanent mutation
_____ ___ oxidizes compounds in blood, usually making _____ toxic
cytochrome P450, less
tumor progression
differentiation of cell usually becoming more aggressive, Darwinian selection, heterogeneous populations, clonal expansion, increasing number of mutations and epigenetic changes
in tumor, cell _______ and cell death
division is uncoupled from cell differentiation
_____: studies have shown cancer rates differ _____, not usually by ethnic background
environment, geographically
Carcinoma
epithelial
what do oncogenes involve in
excessive amount of molecule, abnormal function of molecule
angiogenesis
feeds blood to tumor as it grows
what are examples of growth signaling components
growth factors, receptors, GTP-binding proteins, nonreceptor kinases, transcription factors, cell cycle and apoptosis regulators
overcoming requirements for _____ _____, by short circuiting _____ _____ mechanisms, including defects in signal transduction
growth factors, surface receptor
Rag2 knockout mice
have no functional lymphocytes, and develop more tumors, immune system more effective vs virus-induced cancers
_______ detect binding, if none destruction by _______ (as opposed to _______)
integrins, apoptosis, necrosis
what are the three steps of metastasis
invade tissue to access blood or lymph, travel in fluid system, and leave fluid system, grow in remote tissue or organ
metastasis
invades bloodstream and travels
what are two mechanisms of cell spreading
invasion, metastasis
cancer cells block pathways _____
leading to apoptosis, and this can be the actual mechanism of cancer in some cell types
tumors must "_____" not to produce _____ _____
learn, foreign antigens
_____: (such as smoking or working as a chimney sweep) affect cancer rates
lifestyle
A549 cells
lung, adenocarcinoma cell in human (secretory capacity in epithelial cancer)
what another location common for metastatic activity
lungs, liver, stomach, intestines
lymphoma
lymphatic tissue, solid tumors
cancer cells invade _____ system, becoming lodged in _____ _____, common location for _____ _____
lymphatic, lymph node, metastatic tumors
point mutation
many (up to 30%) human cancers from mutation of Ras (small monomeric G protein)
tumor (neoplasm)
mass of cells growing without normal control, but not always growing faster than normal tissue
what cells seed new organs to continue cycle?
metastatic cells
benign
mild, not cancerous
what doe metastatic tumors release?
millions of cells per day into blood or lymph
transit amplifying stem cell
more differentiated, but keeps opportunity to divide
L cells
mouse fibroblast
chromosome translocation
movement to more of less expression
J774
murine macrophage cell line
______ is important in developing cancer
mutation
basal layer of skin has cells that when dividing____
one cell keeps division option, stem cell one cell gives up cell division and makes keratin
gene amplification
over expression
_____, crucial regulating molecule for cell division
p53
___ can be damaged by some compounds in smoke (___ controls cell cycle, guardian of genome)
p53, p53
___ is most frequently mutated protein in human cancers, ___ triggers cell cycle arrest, apoptosis, and DNA repair mechanisms
p53, p53
invasion
penetration of tissue
what is perinuclear halo
presence of a vacuolated area that surrounds the nucleus
ability to _____ and _____ causes cancer
proliferate, move
uncontrolled _____ is defining for cancer, but _____ __ _____ is also crucial for disease
proliferation (rapid increase of numbers), ability to spread
some cancer cells increase production of _____ (like _____) needed to erode tissue (like _____ _____ adjacent to epithelial cells) to facilitate penetration and migration
proteases, plasmin, basal lamina
_____ are normal, but can be dysregulated (to oncogenes) and cause cancer or can be brought into cell by virus. _____ cell proliferation, _____ cell survival
proto-oncogenes, increased, increased
_____ must be converted to _____ to become _____
proto-oncogenes, oncogenes, carcinogenic
promotion
repeated exposure to certain triggers such as croton oil that contains phorbol esters, hormones or growth factors
immune surveillance theory:
restricts growth of tumors cells, suggests tumors are common but body seeks and destroys them, immune suppressed patients have more cancers
first tumor suppressor gene
retinoblastoma (RB) gene, found in family with trait
density-dependent inhibition of growth
seen in cell culture systems in the lab
experiments with nude mice
showed ability to implant tumors, these lack a functional immune system bc no thymus or T immune cells (no adaptive immune response)
cancer cells die at all points of the cycle...
showing they were not halted at restriction point
two-hit hypothesis
since we have two genes, may require two mutations ("Sully" and flt 1549)
what is a koliocyte
specific cellular events caused by infection with HPV
Vascular endothelial growth factor (VEGF)
stimulates angiogenesis from existing vessels
What is helicobacter pylori?
stomach cancer
epidemiology
study of causes of disease
sarcoma
supporting, tissue, cartilage, fat, bone, muscle
maintenance of _____, expression of _____, important in development of cancer
telomeres, telomerases
What can UV light cause?
thymidine dimers, leaves signature of sunlight damage in p53 gene found in skin exposed to sun, simply sign of damaged or cause of cancer
_____ and _____ tumors selects for cells more capable of being metastatic
transport, re-establishing
local DNA rearrangement
two genes can be combines, Philadelphia chromosomes
cell differentiation (senescence)
usually limit cell division capacity
cancer cells produce _____ and _____ stimulate vessel growth
vascular endothelial growth factors, fibroblast growth factor
Hepatitis B and C
virus causes liver cancer
leukemia
white blood cells in general, fluid tumors