Cell Cycle Regulation and Cancer

Cell Cycle Regulation, Apoptosis, and Cancer

• Cell division progresses to the next stage (S).
• Some cells enter a G0 stage, a non-dividing state.
• Some cells can re-enter the cell cycle.
• Stages in the cell cycle are regulated by signals.
• DNA replicates in the S phase.
• Other synthesis and translation of proteins occurs.
• Cells prepare for division in the G2 phase.

Variations in Cell Cycle

• Certain cell types divide continuously to replace dying cells (e.g., epithelial cells in the gut).
• Cells in mature tissues like nerve and muscle tissue generally don't divide after maturity.
• Liver cells and lymphocytes divide only when prompted.

Cell Cycle Duration

• Adult tissues have a cell cycle of approximately 20 hours.
• Embryonic cells have a very short cycle (< 30 minutes).

Cleavage of a Fertilized Egg

• Zygotes divide rapidly without significant cell growth, resulting in smaller cells.

Regulation of Cell Cycle by TOR

• TOR (Target of Rapamycin) regulates cell growth and cell cycle progression.
• Increasing protein synthesis leads to increased cell mass.
• Cell growth is regulated by TOR.
• TOR inhibits protein synthesis and prevents excessive proliferation.

G2-M Transition

• Cell size, DNA replication status, and DNA damage are checked.
• Growth factors also play a role.

G2-M Transition Checkpoints

• Check for DNA damage or errors in replication.
• Ensure proper cell size.

G1-S Transition

• A cell is checked for growth factors and nutrients before proceeding.
• Presence of sufficient nutrients and growth factors is crucial.
• DNA damage is checked for.

Cell Cycle Checkpoints

• G1 checkpoint: Checks if the cell is healthy and adequate resources are present.
• G2 checkpoint: Checks for DNA replication completion and DNA repair.
• Spindle checkpoint: Ensures all chromosomes are attached to spindle fibers before mitosis proceeds.

Mitotic Spindle Checkpoint

• Prevents anaphase initiation if all chromosomes are not properly attached to the spindle fibers.
• This prevents mis-segregation of chromosomes.

Cell Cycle Regulation and Cancer

• Oncogenes are genes that promote cell growth and division.
• Tumor suppressor genes inhibit cell growth and division.
• Mutations and/or loss of function in tumor suppressor genes can contribute to uncontrolled cell growth and tumor development.

Apoptosis (Programmed Cell Death)

• A programmed process involving a series of steps to eliminate unwanted or damaged cells.

Extrinsic Pathway of Apoptosis

• Signals from outside the cell trigger programmed cell death.

Intrinsic Pathway of Apoptosis

• Triggers within the cell initiate programmed cell death.

Caspases

• Hydrolytic enzymes involved in apoptosis, cutting proteins into smaller pieces
• Initiator and executioner caspases.
• Crucial for initiating a signal cascade.

Necrosis

• A type of cell death caused by injury or damage.
• Cellular contents leak into the surrounding environment (unlike apoptosis).
• Triggers an inflammatory response in surrounding tissues.

P53

• Tumor suppressor gene involved in regulating cell growth and repairing DNA damage.
• Activated by DNA damage and triggers apoptosis or cell cycle arrest.
• Inactivation or mutations negatively impact apoptosis regulation.

Tumor Suppressor Genes/Oncogenes

• Loss-of-function mutations in tumor suppressor genes lead to unchecked cell growth.
• Gain-of-function mutations in oncogenes lead to abnormally high cell growth.
• Both factors play a role in cancer development.

RB (Retinoblastoma) Gene

• Involved with inhibiting cell division.
• Inactivation can result in uncontrolled cell growth.
• Hereditary vs sporadic RB variants/mutations
• Genes controlling cell cycle progression are regulated through the RB pathway.

Explore the intricacies of cell cycle regulation, apoptosis, and their implications in cancer biology. This quiz covers various stages of the cell cycle, the differences in cell division among different cell types, and the role of TOR in regulating these processes. Test your knowledge on how these mechanisms contribute to normal and cancerous cell growth.