Flashcards in Exam 4 Lesson 42 Deck (54):
How are cancers classified?
Based on tissue of origin
Cancers arising from epithelial cells (most common)
Cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue
Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of abnormal blood cells
Lymphomas and myeloma
Cancers that begin in the cells of the immune system
Arise from the cells that produce the dark pigment in skin, hair
Substances that cause DNA mutations that cause cancer
Non- hereditary cancer
Somatic mutations cause most cancers
Germline mutations , rare (~5% of cancers)
What kind of disease is cancer?
A genetic disease. Caused by gene mutations.
Where do most cancers originate?
From a single aberrant cell
What kind of mutations cause cancer?
cancer is caused by a progressive accumulation of random mutations in a single lineage of cells
clonal evolution theory
Accidental production of mutant cell
Cell proliferates and there are two mutations
Cell proliferates and there are three mutations
Can lead to dangerous cell proliferation
What are the two kinds of mutation events?
Genetic change and epigenetic change
What are the two kinds of genetic changes?
Small scale and large scale
Small scale genetic changes
A small gene in one or a few nucleotides; point mutation, insertion, deletion
Large scale genetic changes
In chromosomal structure; duplication, amplification, deletion, insertion, inversion, translocation
Histone modification (heterochromatin pathway; not inherited);
DNA methylation (an inherited pattern of methylation of C nucleotides in CpG sequence)
What is Gleevec?
A drug that targets a protein kinase that promotes development of leukemia.
What are oncogenes?
They have a gain-of-function mutation. They produce overactive proteins that drive the cell cycle or contribute to some other aspect of the cancer process.
What are tumor suppressor genes.
They suffer a loss-of-function mutation. The loss of both copies of the normal gene leads to cancer. Loss of gene activity may come from a genetic change or an epigenetic change.
What causes loss of gene activity?
A genetic change or an epigenetic change
Evolution of a normal cell into a tumor cell. A process by which normal cells are transformed into cancer cells.
Evolution of benign into a malignant cancer cell. Cancer cells break loose, enter blood or lymphatic vessels, and form secondary tumors at other sites in body.
Six proposed hallmarks of cancer
1. Self- sufficiency in growth signals
2. Insensitivity to anti-growth signals
3. Evading apoptosis
4. Tissue invasion and metastasis
5. Limitless replicative potential
6. Sustained angiogenesis
What does cell proliferation require?
1. Progression through the cell cycle
2. Cell growth
What do normal cells require for proliferation?
Signals in the form of cytokines, ECM components, and cell-cell interactions.
How do cancer cells proliferate?
They generate their own cell proliferation signals (mutagens, growth factors) or they recruit nearby stromal cells, causing them to release growth factors.
Receptors for mutagens or growth factors that may be unregulated. Downstream signaling molecules that may be unregulated like mutant form of Ras, mTOR, or Akt.
What loss of function mutations promote proliferation pathways?
Loss of function mutations in Rb and PTEN
What do anti-proliferative and anti-growth signals usually block?
The inactivation of Rb
What happens if Rb is active?
It inhibits E2F and expression of S-phase genes
How are cancer cells insensitive to anti-growth or antiproliferation signals?
They may downregulate receptors for anti-proliferative signals, have loss-of-function mutations in Cdk inhibitors or loss of function mutations in Rb
What is role of p16, or p15INK4?
It inhibits CDk4 from binding to cycling D, inhibiting the complex
What is role of apoptosis?
It maintains constant cell number and eliminates cells that have become abnormal because of genetic mutations or other stresses.
What does p53 protein do in response to DA damage and stress?
1. Controls cell cycle arrest
2. Controls apoptosis
What does p53 bind to?
It binds to regulatory region of p21 gene. p21 is a Cdk inhibitor protein.
Why does FAK interact with growth factor receptors?
To control the ERK/MAPK pathway in regulation of cell proliferation.
Do animal stem cells need to attach to lamina?
Yes. They must to survive apoptosis signals.
Why do somatic cells have a finite replicative potential?
Because of a lack of telomerase activity. Telomeres shorten with each replication cycle.
As telomeres shorten, chromosomal ends become unprotected, leading to cell cycle arrest.
How do cancer cells maintain replicative potential?
Normally, telomerase expression is largely repressed in postembryonic cell lineages. Cancer cells are able to maintain the expression of telomerase for continued telomerase activity.
From cell into a capillary or lymph vessel
From capillary or lymph vessel into cell
How is success rate for each step in metastasis?
What must new tumors in new locations do?
Recruit a blood supply and recruit surrounding cells to create a "niche"
Epithelial-mesenchymal transition (EMT)
Shutdown of E-cadherin expression enables cancer cells to extricate themselves from the keratinocyte neighbors in the epidermis, while its replacement by expression of N-cadherin allows these tumor cells to interact with mesenchymal cells
How are normal epithelial cells kept in place?
By cell-cell and cell-ECM interactions
What do cancer cells do to cell-cell and cell-ECM interactions?
They alter these interactions via changes in gene expression. For example, they alter cell-cell adhesion molecules (CAMs), by losing E-cadherin and gaining N-cadherin.
Growth of new blood vessels from pre-existing vessels
Why do tumors rely on angiogenesis?
They increase in size and need new blood vessels to supply all cells with oxygen and nutrients.
How do cancer cells respond to hypoxia?
They release factors that stimulate the proliferation of endothelial cells.
Positive factor for angiogenesis