Question

Cell Biology Tutorial: Introduction to Oncology

Answer 1

\({\bf{Basic~Terminology:}}\)
- oncology: the study of tumor formation and other aspects of cancer
- proto-oncogenes: genes that are the pre-cursors for oncogenes
- oncogenes: genes responsible for excessive cellular growth through increased gene expression or uncontrolled growth
- tumor-suppressor genes: like the name says, suppress growth of tumors
- genome maintenance genes: preserve the genome and resist changes
- oncogenesis: the process by which cancer forms
- carcinogens: chemicals that alter normal genes and induce cancer
- tumor: a growth of cells that lacks the normal mechanisms that restrict growth
- metastasis: migration of a tumor into new sites
- carcinomas: tumors from epithelia/endoderm/ectoderm (more common)
- sarcomas: derived from mesodrm
- leukemias: subtype of sarcomas that live as free cells in the blood
- benign: tumor held together by cell adhesion
- malignant: tumor that spreads/incades other cells
- basement membrane: layer at the bottom of epithelial cells and surrounds blood vessels

\({\bf{Properties~of~Tumors:}}\)
- resist cell death
- signal-induced proliferation
- evasion of growth suppressors
- induction of angiogenesis
- leave rude/irrelevant comments on my tutorials
- replicative immortality
- metastasis

^ those are the major ones, then looking at individual cancer cells:

- hypoxic (low oxygen)
- have a genetic composition different to that of normal cells
- depend on proteome maintenance pathways
- rely on glycolysis regardless of oxygen content (Warburg effect)
- use telomerase to extend their telomeres, overcoming the natural limitations on a normal cell's lifespan
- up-regulate growth pathways, down-regulating growth inhibition/cell death pathway

\({\bf{Angiogenesis:}}\) induction of new blood vessels to provide nourishment to the cancer cell
> involves degradation of the capillary membrane and migration of the endothelium into the tumor, forming a new membrane around the capillary
> growth factors like beta-FGF,TGF-alpha, VEGF may be involved

\({\bf{Epithelial-to-Mesenchymal~Transition:}}\)
- requires gene changes that induce changes like loss of adhesion and loss of polarity
- Snail and Twist TF's down-regulate cell adhesion (E-cadherin) and digest the basement membrane

Answer 2

\({\bf{Development~of~Cancer~Cells:}}\)

- direct-acting carcinogens: electrophiles that react with the N and O atoms in DNA, modifying base pairin and inducing mutations
- indirect-acting carcinogens: nonreactive, water insoluble which can induce cancer after being introduced to electrophilic centers, ex. P450 enzyes add electrophilic centers

- irradiation discovered to damage genes (experiments with gamma-irradiated Drosophila)
- smoking (benzo(a)pyrene induces mutations in the lung)

- multi-hit model: cancers arise through clonal selection, e a mutation may give a cell a growth/mutational advantage allowing it to crowd out other cells and bypass tumor suppression
> prediction 1: cells in a tumor should share genetic alterations
> prediction 2: cancer/mutation rate should increase with age b/c mutations take a long time to accumulate

- MYC protein: transcription factor for genes that transition the cell from G1 to S
--> increased MYC transcription may turn proto-oncogenes into oncogenes
- requires continuous production of MYC

- p53 protein: tumor suppressor that halts the clel cycle
- APC: another tumor suppressor
> implicated in mutation of K-ras
- Ras protein: in its hyperactive form, may induce transformation of immortal cells into cancer cells

Answer 3

\({\bf{Genetics~of~Cancer~Formation:}}\)

gain-of-function mutations:
- point mutation (increased gene product)
- chromosomal translocation (formation of hybrid gene with hyperactive protein)
- chromosomal translocation (moves a growth regulator under the control of a different enhancer that changes how the gene is expressed)
- amplification: increased expression of a dna segment


loss-of-function mutations among:
- proteins that regulate entry into cell cycle
- receptors/transducers for hormones that inhibit proliferation
- checkpoint pathway proteins
- apoptotic proteins
- DNA repair enzymes

> mutations in tumor suppressor genes are typically recessive
> exception: haplo-insufficient: having one defective copy of a gene alters the phenotype, ex. RB gene
> loss of heterozygosity: (LOH) inactivation/loss of a normal allele

note: simply inheriting the mutation is not enough to cause cancer; must also inherit the mutations for the other genes involved in cancer development

Epigenetics:
- DNA hypomethylation (increases expression)
- chromatin modification (methylayion, demethylation, acetylation, etc.)

miRNAs: base pairs with the 3' UTR of RNA and inhibits translation
- involved in chronic lymphocytic leukemia (CLL) + prostate cancer, in mice
- can function as oncogenes or tumor suppressors

Answer 4

Anyway, that's the end of my tutorial, I hope it was a helpful resource. Source material is Chapter 24.1-24.3 of Molecular Cell Biology, Eighth Edition, Lodish, et. al.