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Flashcards in Molecular Basis For Cancer Deck (37)
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1
Q

Theory of colonial evolution of cancer

A

. Initial damage/mutation occurs in single cell that allows cells to grow w/ selective growth advantage
. Eventually outgrows neighbor cells
. In colonial population, a single cell may acquire 2nd mutation providing additional growth advantage and allowing it to expand and become predominant cell
. Repeated cycles colonial expansion lead to fully developed malignant tumor

2
Q

Hallmarks of cancer

A
. Self-sufficiency of growth signals 
. Insensitivity to growth inhibitory signals 
. Evasion of apoptosis 
. Limitless replication potential 
. Sustained angiogenesis
3
Q

Self-sufficiency of growth signals in cancer cells

A

. Mutation in GFs that transmit growth signals from 1 cell to another
. Mutation in GF receptors on cell surface
. Mutation in signal tansduction molecules that activate cascade of phosphorylation rxns w/in cell
. Mutation in nuclear TFs
. Allows cell proliferation despite having an inactive growth receptor

4
Q

Porto-oncogenes

A

. Genes whose protein products control cell growth and differentiation
. When they undergo mutations causing qualitative and quantitative changes in gene products they become oncogenes

5
Q

Oncogenes

A

. Genes whose expression results in neoplasticism transformation
. Normally from Porto-oncogenes, but can be from mutations that lead to structural changes or inc. expression
. Dominant

6
Q

Tumor suppressor genes in formation of cancer

A

. Normally inhibit growth
. Loss of gene function from mutations lead to cell transformation by removing restraints that normally regulate growth
. Retinoblastoma tumor suppressor, p53, BRCA1 and 2 are examples
. Recessive

7
Q

P53 functions

A

. Regulator fo gene expression and control genes in growth regulation
. Role in DNA repair through G1 arrest until damage is repaired
. Controls apoptosis by triggering it if cell damage is beyond repair

8
Q

How does a cell get limitless replication potential?

A

. Reappearance of enzyme telomerase

9
Q

P53 role in angiogenesis

A

. Directed synthesis of anti-angiogenic factor thrombospondin to restrict ability of cells to induce angiogenesis
. When p53 mutates, antiangiogenic factor is no longer made and angiogenesis cans occur

10
Q

Proliferative cells metabolize glucose primarily through ____

A

. Glycolysis

. Excrete a large amt of carbon in form of lactate or other metabolic acid

11
Q

T/F cell won’t uptake nutrients unless stimulated by growth factors

A

T, cancer cells overcome this through genetic mutations that alter receptors so here is constitutive uptake and metabolism of nutrients

12
Q

Warburg effect

A

. In presence of O2 most differentiated cells metabolize glucose to CO2 via oxidative phosphorylation
. Most cancer cells produce large amount of lactate regardless of availability of O2 (aerobic glycolysis)

13
Q

Why do proliferating cells switch to less efficient metabolism?

A

. For cells to proliferate the bulk of glucose can’t be committed to catabolism for just ATP production, if it was ATP ratio would be too high impairing flux of glycolytic intermediates limiting acetyl CoA and NADPH required for macromolecule synthesis
. Glycolytic oxidation provides energy and raw materials required for production of new cells

14
Q

Normal resting cells use ___ to satisfy requirements cells

A

. Catabolic metabolism

. Met through fatty acid oxidation and oxidative metabolism of glucose

15
Q

Upon growth factor stimulation, proliferation cells inc. uptake of ____

A

Glucose and glutamine

16
Q

Glutamine importance in cell proliferation

A

. Gln most abundant FAA in human serum
. Use as N donor for biosynthesis of nucleotides and non-essential AA
. Carbon source for replenishment of TCA intermediates that are diverted in various anabolic pathways during proliferation

17
Q

Activation fo growth receptors lead to _____

A

. Tyr kinase signaling
. PI3 kinase activation
. Promotes survival and growth

18
Q

PI3kinase pathway promotion of survival and growth

A

. Stimulates glucose uptake and flux through early part of glycolysis

19
Q

Tyrosine kinase signaling role in cell proliferation

A

. Prevents further oxidation of glucose through TCA cycle

. Makes glycolytic intermediates available for macromolecular synthesis and supports NADPH production

20
Q

C-Myc drives uptake and metabolism of ___

A

. Gln

. Supports NADPH production

21
Q

Stem cell theory of cancer

A

. Tumors contain cancer stem cells w/ indefinite proliferative potential
. Self-renewing and responsible for all components of a heterogenous tumor
. Cells are drug-resistant and express markers typical of stem cells
. Responsible for tumor reoccurrence years after successful treatment

22
Q

Inherited mutations in tumor suppressor genes account for ____ of human cancers

A

5-10%

23
Q

BRCA1

A

. Accounts for 50% women w/ hereditary feast cancer.
. Mutations result in hereditary syndrome of breast and ovarian cancer
. Inc. risk of breast cancer at younger age
. Bilateral cancers more common

24
Q

BRCA2

A

. 30% families w/ inherited breast cancer
. Risk similar to BRCA1
. Cancer occurs at early age and involves both breasts
. Play role in repair of double stranded DNA breaks

25
Q

Adenomatous Polyposis Coli (APC)

A

. Gene found in 5-10% colorectal cancer
. Account for familial adenomatous polyposis (FAP) syndrome
. Multiple polyps found at very yong age (10-20y/o)
. Normal role is inhibition of beta-catenin
. When mutated beta-catenin freely moves into nucleus and activates cell proliferation and invasion

26
Q

Beta-catenin functions

A

. Involved in cell-cell adhesion and activation of signaling pathways
. Normal maintained at cell surface tethered to cadherins present on cell surface

27
Q

Hereditary nonpolyposis colorectal carcinoma (HNPCC)

A

. Disease which transformation from polyp to carcinoma is rapid but rate of polyp formation is normal
. Predisposition due to inherited mutations in mismatch repair genes

28
Q

c-Myc characteristics

A

. Helix-loop protein
. Inc. Gln transporters
. Induces glutaminase activity
. Gln addiction occurs when c-myc is activated

29
Q

Tumor initiation

A

. Exogenous or endogenous carcinogen induces alteration in genetic makeup of cell
. Results in mutation w/in 1 or few cells that confers potential for neoplasticism growth

30
Q

Tumor promotion

A

. Alterations in gene expression and cell proliferation transform initiated cell into discernible population of cancer cells
. Mediated by chemicals that have no appreciable carcinogenic potential of their own
. Greatly enhance tumor development when exposed to carcinogens for long periods of time

31
Q

T/F some chemical are activated to carcinogens in body and some are detoxified by enzymes

A

T

32
Q

Enzymes important for metabolizing chemicals w/in body

A

. Cytochrome P450 oxidase
. N-acetyl transferase
. Glutathione transferase

33
Q

Carcinogen interaction w/ DNA

A

. Carcinogenic residues bound to DNA provide fingerprint of exposure and indicator of carcinogenic damage

34
Q

Well known environmental carcinogens

A

. Poly cyclic aromatic hydrocarbons (PAH)
. Aromatic amines
. Both from cigarette smoke
. Major etiologies factors in lung, bladder, and breast cancers

35
Q

What helps explain difference in susceptibility w/in populations for carcinogens?

A

. Polymorphism in drug metabolizing enzymes

.

36
Q

Specific p53 codon mutation seen in what cancers when benzpyrene adducts bind to DNA?

A

. Lung
. Head
. Neck cancer

37
Q

What cancers are more likely to occur in geographic areas where aflatoxins and hep B are there?

A

. Liver tumors

. Mutations in codon 249 AGG to AGT seen

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