What is the definition of the genetic hypothesis of neoplasia
Acquisition of non-lethal genetic damage (mutations)
A group of disorders that are based on accumulated genetic events which alter normal replication
chromosomal breakage, translation, point mutation
Sources of genetic damage
Age, environment, family
Factors that may lead to neoplastic cells
Specific mutations occur or inherited mutations, genomic instability of cancer cells, altered cell differentiation, uncontrolled cell proliferation
What is fundamental to cancer growth?
cell cycle abnormalities
What ic a central cause of malignant transformation?
The loss of normal cell-cycle control
What are the two steps in cell proliferation
DNA replication and cell division
What are the steps in normal cell proliferation?
1. Binding of growth factor 2. transient activation of growth factor receptor 3. Signal transduction to nucleus 4. Activation of nuclear regulatory factors 5. Entry into cell cycle
What is cell differentiation?
The cellular aquisition of specialized function
What does cellular differentiation involve?
procurer stem cell, cell replication, gene expression
What are dominant or "proto-onocogenes"
What are recessive oncogenes
tumor suppressor genes
What happens when apoptosis is misregulated?
Cells that don't die when they should may become neoplastic
How do we regulate target genes?
Anywhere along the pathway of cell differentiation?
What are the processes that may cause dysregulation that lead to cancer?
Carcinogenesis, physiological alterations, multiple DNA damaging events that are not repaired
T/F Carcinogensis can occur due to a single step
False--multi-step process, with different errors leading to different cancers even within the same organ
T/F Can a single mutation fully transform a cell
NO, though a single change may indicate future issues
T/F Most cancers involve the change in a single oncogene or tumor suppressor gene
False--Most cancers involve several oncogenes and loss of two or more tumor suppressor genes
How do gene changes lead to dysregulation?
New proteins produced by changed genes may lead to the changes that cause cancer
What are the general classes of growth signals that affect cellular regulation?
1) Self-sufficiency in the absence of growth signals 2) Insensitivity to growth-inhibitory signals 3) Evasion of apoptosis 4) Defects in DNA repair 5) Limitless replicative potential 6) Sustained angiogenesis 7) Ability to invade and metastasize
Which factors may affect self-sufficiency?
1) Growth factors 2) Growth factor receptors 3) Signal transduction proteins 4) Nuclear regulatory proteins 5) Cell-cycle regulators
What is meant by a stuck accelerator?
Growth regulating signals are disrupted and the cell becomes self-sufficient in its reproduction.
What is meant by no brakes?
Insensitivity to growth-inhibitory signals.
Give an example of growth-inhibitory signals
nuclear regulatory proteins, transcription factors, inhibitory proteins (RB, BRCA-1, p53)
What causes the evasion of apoptosis?
Over expressed anti-apoptotic genes or altered pro-apoptotic genes
What happens when BCL-2 is over-expressed?
BCL-2 is anti-apoptotic so cell is able to evade apoptosis
What can happen if p53 is faulty?
p53 is pro-apoptotic so a faulty gene would permit cell survival
What are the consequences of faulty DNA repair?
May lead to defects in other genes. If inherited may cause genomic instability syndrome
What is limitless replicative potential?
typically due to increased telomerase activity which PREVENTS the natural aging of the gene. in 90% of human tumors
What are the consequences of telomere shortening?
Senescence and apoptosis (cell aging)
What leads to sustained angiogenesis?
The ability to feed self --production of growth factors necessary for vascularization that may not be an original function of the cell
Describe the changes that allow metastases?
Altered cell adhesion molecules. Extracellular degradation enzymes
What is the consequence of the acquisition and accumulation of non-leathal genetic damage?
What happens when cell cycle regulation is disrupted?
The cell changes in proliferation and differentiation
Why do we care about molecular mechanisms of carsinogenesis?
Provides a better understanding for treatment and prevention