Neoplasms Flashcards
neoplasia
new growth
neoplasm
the growth itself
differentiation
determination of cell’s fate, specialization
proliferation
cell division and growth of new cells
apoptosis
programmed death, remodeling
benign vs malignant tumors
- When differentiated cells mutate, they form differentiated tumors— benign tumors
- When undifferentiated cells mutate, they form rapidly dividing tumors— malignant tumors
phases of cell cycle
- G1 (gap 1) – postmitosis – 0 DNA synthesis, cell growth phase
- DNA Synthesis (S phase)
- G2 (gap2) – premitosis, 0 DNA synthesis
- M – mitosis
- G0 – quiescence, resting phase
checkpoints in the cell cycle
- Three major checkpoints are found in the G1, G2 and M phases
- For many cells, the G1 checkpoint seems to be the most important, “restriction point”
- If a cell receives a go-ahead signal at the G1 checkpoints, it will usually complete the cycle and divide
- If it doesn’t, it will switch into a nondividing state called the G0 phase
- Nerve and muscle cells never divide. Other cells, such as liver cells, can be “called back” to the cell cycle by certain environmental cues, such as growth factors released during injury
permanent cell vs stable cell
- permanent = cant undergo cell division –> always in G0
- stable = can be called back into division –> can go from G0 to G1
protein kinases and cyclins
- Particular protein kinases give the go-ahead signals for mitosis
- To active such a kinase, it must be attached to a cyclin.
- Therefore they are called cyclin-dependent kinases or Cdks.
- For instance, there is a cyclin that rises during S and G2 phases and then falls abruptly during M phase. It attaches to a Cdk and creates a complex called MPF (maturation promoting factor)
- Thus we can think of MPF as “M-phase promoting factor”
- During anaphase, MPF helps switch itself off by initiating a process that leads to the destruction of its own cyclin.
G1 checkpoint
-there are at least three CDK proteins and several cyclins at this checkpoint
genes that control the checkpoints
- Genes that turn off or decrease the rate of cell division (Tumor suppressor genes)
- Genes that turn on or increase the rate of cell division (Proto-oncogenes)
tumor suppressor genes function
- Some tumor suppressor proteins normally repair damaged DNA
- Some tumor suppressor proteins control the adhesion of cells to each other or to the extracellular matrix; proper cell anchorage is crucial in normal tissue
- Other tumor suppressor proteins are components of cell signaling pathways that inhibit the cell cycle.
proto-oncogene
- Genes that code for normal proteins used in cell division (Growth factors, Growth factor receptors, G proteins, Enzymes that produce second messengers, Genes that turn the production of these proteins on and off)
- Mutated form of a proto-oncogene is called oncogene
- Oncogenes promote cancer
two key genes for controlling cell division
- Ras proto-oncogen
- p53 tumor suppressor gene
Mutation in ras occurs in about 30% of human cancers
Mutation in p53 in more than 50%
tumor suppressing gene - p53
-The protein coded by this gene is called p53 as well.
-In at least three ways, p53 prevents a cell from passing on mutations due to DNA damage
1. This protein indirectly blocks the ability of cyclins
p53 induces the expression of another gene called P21.
p21 inactivate Cdk.
2. p53 protein can directly turn on genes involved in DNA repair
3. When DNA damage is irreparable, p53 activates “suicide” genes, whose protein products cause cell death by apoptosis.
-Normal function of TP53 inhibits angiogenesis necessary for tumor development
Li-fraumeni syndrome
-mutation of p53 on chromosome 17, with high rate of many types of tumor
tumor suppressor gene: Rb
- Rb gene prevents the cell from entering S-phase until the appropriate growth signals are present
- Mutation of Rb gene on chromosome 13→ Retinoblastoma, cancer of the retina
