1. Cell-cell communication,
2. Regulated cell growth,
3. Cell division,
4. Cell differentiation,
5. Cell death,
6. Cell movement,
7. Cell adhesion
Development and maintenance of a multicellular organism depends on numerous regulatory pathways. What are they?
Cell-cell communication, regulated cell growth, cell division, cell differentiation, cell death, cell movement, and cell adhesion are misregulated in what kind of cells?
Mouse model systems
What kind of animal model systems do scientists use to introduce oncogenes, in order to understand their function?
Not all mice expressing a single oncogene acquire tumors. Does the combination of two oncogenes significantly increase or decrease tumor formation?
Additional accidental changes are required for tumor formation
Tumor formation takes time suggesting what?
The cancer critical gene
Tumor suppressor genes have also been studied by deleting the gene for what?
Will mice with a single copy of a tumor suppressor gene deleted accumulate cancerous tumors at a higher frequency?
Growth, division and death
The 'normal' versions of cancer causing genes are involved in signaling pathways that regulate a cells 'social' behavior including what?
1. Transmembrane receptors,
2. Signaling proteins,
3. Intracellular GTP-binding proteins,
4. Protein kinases,
6. Gene regulatory proteins
Proteins encoded by proto-oncogenes and tumor suppressor genes include what?
Cell growth, DNA replication and cell division
Mutation of proteins encoded by proto-oncogenes and tumor suppressor genes disrupt normal signaling pathways creating proliferative signals to switch on what?
In the same signaling pathway
Often mutations in tumor suppressor and oncogenes have been found where?
Active Rb protein binds to E2F family members to block expression of downstream genes. These downstream genes encode proteins responsible for entry into what?
The p16 protein
In nonproliferating cells, Rb is in its unphosphorylated 'active' state through the activity of what?
When the cell receives the correct signals, the levels of active G1-Cdk increases leading to phosphorylation of what?
The expression of genes needed for entry into S-phase
Phosphorylated Rb is inactive, releasing E2F proteins to promote what?
Cdk4 or Cyclin D genes
Some glioblastomas and breast cancers have been linked to overexpression of what?
Smaller cells with each successive division
Cell cycle progression without cellular growth results in what?
Mitogen mediated signals and growth factor mediated signals
What are two types of extracellular signals required to drive a cell through the cell cycle?
Growth factor mediated signals
What signals are required for the uptake and utilization of nutrients?
Inappropriate cell growth
Continued growth of a cancer therefore also requires heritable changes that induce what?
The PI-3 kinase/Akt intracellular signaling pathway is activated by what kind of signals: extracellular or intracellular (e.g. insulin and insulin-like growth factors)?
Activation of receptor tyrosine kinases activate PI3 kinase which in turn leads to the activation of what?
Protein synthesis is increased; Glucose uptake is stiumulated
Through its effect on mTOR, what is increased? What is stimulated?
Through its effect on mTOR, protein synthesis is increased and glucose uptake is stimulated leading to increased what?
Dephosphorylating substrates phosphorylated by PI3 kinase therefore buffers Akt activity
PTEN is responsible for what?
Hyperactivation of this signaling pathway
Loss of PTEN leads to increased Akt levels, which leads to what?
Over stimulation of this pathway explains the observation that tumor cells exhibit increased rates of what?
High rates of glucose uptake coupled with high levels of pyruvate excretion
What is used to identify tumors?
When they have sensed DNA damage or the absence of extracellular survival signals
When do animal cells undergo apoptosis?
Inappropriate overexpression of Bcl2 (translocation event) is responsible for what
p53 (the cellular stress sensor)
What is another apoptosis control gene identified in cancer besides Bcl2?
In response to hyperproliferative signals, DNA damage, hypoxia, or telomere shortening, do the levels of p53 increases or decreases?
Cell cycle arrest or apoptosis
Stable and activated p53 triggers the transcriptional activation of genes whose proteins are involved in what?
1. Stimulate the expression of pro-apoptotic genes
2. Binds to anti-apoptotic factors to block their activity
What are the functions of p53?
1. Loss of p53 allows cells to progress through the cell cycle with DNA damage,
2. Loss of p53 allows cells to escape from apoptosis,
3. Loss of p53 promotes genetic instability which promotes the accumulation of DNA
4. Loss of p53 makes cells more resistant to anticancer drugs and irradiation
The loss of p53 promotes cancer for what 4 reasons?
Double stranded DNA viruses
What are capable of surviving in host cells as extrachromosomal plasmids that replicate along with the host cell chromosomes?
What is a DNA tumor virus identified as the causative agent of uterine cervical cancer
The papillomavirus exists in the basal layer of the cervical epithelia as what?
Benign growth or wart
A switch to a replicative phase (papillomavirus) occurs in the cells of the outer epithelium resulting in continued cell growth and the formation of a what?
The viral genes integrate into the host chromosome and become active within the basal layer (location of stem cells)
How can cancer result from a papillomavirus?
Viral proteins (E6 and E7)
What proteins can interact with many host cell proteins blocking their activity?
E6 and E7 bind to tumor suppressor proteins to shut down their activity promoting what?
Uncontrolled DNA replication and cell division
E7 binding prevents Rb from binding to and inhibiting the activity of the E2F family of gene regulatory proteins leading to what?
Cdk activity and unchecked cell cycle progression
E6 binding triggers p53 protein degradation leading to an increase in what?
Tumor cells must escape their parent tissue, travel
through the circulation, and colonize a remote site
How does metastasis work?