Cellular Reproduction: Cancer cells and Stem Cells Flashcards
(49 cards)
Four discrete phases in eukaryotic cell division cycle::
1) G1 phase (Gap 1)- interval between M and S-phase.
▪ Cells are metabolically active and continuously grows
2) S-phase (synthesis phase)- DNA synthesis and chromosome
duplication.
3) G2 phase (Gap 2)- cell replenishes its energy stores and
synthesizes proteins necessary for mitosis and cytokinesis.
4) M phase- A nuclear division (mitosis) followed by a cell division
(cytokinesis).
Length of cell cycel
▪ Total time: ~ 24hr
Cell cycle longest phase
▪ G1 phase is the longest phase (~ 10hr).
What is G0 phase
▪ G0 phase: Cells exit G1
to enter a of the cycle called G0
, quiescent stage
➢ Metabolically active but no longer proliferate unless stimulated by
appropriate extracellular signals.
➢ Non-proliferative phase (G0) may be a temporary condition
(quiescence).
What cells cease division and what cells only divide occassionally?
▪ Some cells in adult animals cease division altogether (e.g., nerve cells)
▪ Many other cells divide only occasionally, to replace cells lost because of
injury or cell death.
▪ E.g., cells of skin fibroblasts, cells of internal organs, such as the liver,
kidney, and lung
What do Specific Cyclin and Cyclin-dependent kinases (CDKs) complexes do?
▪ Specific Cyclin and Cyclin-dependent kinases (CDKs) complexes
drives the cell cycle progression during specific stages.
When do Quiescent cells exit ?
▪ Quiescent cells exit G0 phase after mitogen stimulation.
What is Cyclin D-CDK4/6
▪ Cyclin D-CDK4/6 complex is active in the G1 phase and drives the
cell cycle past the G1 checkpoint
What do CDK inhibitors (CKIs) do
CDK inhibitors (CKIs) have been authorized for the treatment of
cancer.
What do CycD-CDK4/6 complexes do?
CycD-CDK4/6 complexes phosphorylate and inactivate proteins such
as Rb, promoting transcription of genes for S phase progression
Cell cycle checkpoints
▪ A checkpoint is a stage in the eukaryotic cell cycle at which the cell examines internal and external cues and
“decides” whether or not to move forward with division.
What happens with multiple checkpoints
▪ Multiple checkpoints and inhibitors: halt cell cycle progression in the absence of appropriate environmental
stimuli.
▪ There are a number of checkpoints, but the three most important ones are:
G1 checkpoint, at the G1/S transition.
* Cell size.
* Nutrients.
* Molecular signals.
* DNA integrity.
G2 checkpoint, at the G2/M transition.
* DNA integrity.
* DNA replication
▪ The spindle checkpoint, at the transition from metaphase to anaphase
What is Retinoblastoma protein (Rb) and the transcription factor p53
▪ Retinoblastoma protein (Rb) and the transcription factor p53 are key checkpoint proteins.
What is Rb
▪ Rb: major G1 checkpoint, blocking S-phase entry and cell growth.
▪ Activity regulated by post-translational modification (phosphorylation).
▪ Unphosphorylated Rb, regulates G0 cell cycle exit and cell differentiation.
What is p53
▪ p53: can halt cell division in both the G1 and G2 phases of the cell division cycle
▪ Most potent cell cycle checkpoint
▪ In response to DNA-damage, p53 triggers cell cycle arrest, cellular senescence, and/or apoptosis
How can cancer occur
▪ Loss of control of the cell cycle- a critical step in cancer development.
▪ Mutations of two types of cell cycle regulators may promote the
development of cancer.
What are oncogenes and proto onco genes
▪ The overactive (cancer-promoting) forms of these genes are called oncogenes,
while the normal, not-yet-mutated forms are called protooncogenes
What are positive and negative regulators?
Positive cell regulators such as cyclin and Cdk perform tasks that advance the cell cycle to the next stage.
Negative regulators such as Rb, p53, and p21 block the progression of the cell cycle until certain events have occurred.
What are tumour suppressor genes
▪ Tumor suppressors: Genes that normally block cell
cycle progression
▪ Prevent the formation of cancerous tumors when they
are working correctly
What is Radiotherapy or Chemotherapy:
▪ Radiotherapy or Chemotherapy: Generating excessive
levels of DNA damage, result in catastrophic levels of
genome instability to induce cell death in cancer cells than in
healthy cells
Targeting CDKS
▪ Targeting CDKs as an effective pharmacological therapy
against cancer proliferation.
▪ CDK inhibitors (CKIs) selectively targeting cancer cells with
abnormal CDK activity as potential therapeutic.
What are stem cells
- Stem cells are able to massively expand in numbers through rapid cell division (self-renew).
- Differentiation or specification of stem cells occurs as a consequence of cell division.
What are totipotent stem cells
▪ Totipotent Stem Cells: Capable of developing into any cell type in the body, including placental cells
