Unit 5.3 - cell cycle control and tumors_SD_MM

Unit 5.3: Control of the Cell Cycle and Tumors

Learning Objectives

  • Describe how cells progress from one stage of the cell cycle to the next.

  • Describe the importance of cell cycle control and checkpoints.

  • Discuss the role of proto-oncoproteins and tumor suppressor proteins at checkpoints.

  • Predict the consequences of non-functional tumor suppressor proteins or hyper-active proto-oncoproteins.

  • Contrast cancer versus benign tumors and discuss the role of exposure to mutagens in the development of tumors.

The Cell-Cycle Control System: 3 Checkpoints

  • G1 Checkpoint:

    • Checks if environment is favorable to proceed to S phase.

    • Asks: Is DNA damaged?

  • G2 Checkpoint:

    • Checks if all DNA has been replicated and if there is any damage that needs repair.

  • M-phase Checkpoint:

    • Checks if all chromosomes are properly attached to the mitotic spindle.

  • Cell Cycle Phases:

    • G1, S, G2, and M phases.

Transition Through Cell Cycle Phases

  • Different cyclin proteins regulate transitions between cell cycle phases.

  • Cyclins and Cyclin-dependent Kinases (Cdks):

    • Cyclins rise in concentration towards the end of each phase.

    • Cyclins bind to and activate Cdks, promoting phase transitions.

G1 Checkpoint Details

  • The G1 Checkpoint:

    • It is the "master" checkpoint critical in preventing tumors.

    • Controlled by Proto-oncogenes (promoting division) and Tumor Suppressor proteins (halting division).

  • Process at G1 Checkpoint:

    • Promoting Cell Division:

      • Proto-oncoproteins ensure cells transition into S-phase.

    • Preventing Cell Division:

      • Tumor suppressor proteins can halt the cycle or induce apoptosis.

Malfunctions Leading to Tumor Formation

  • Two Main Malfunctions:

    1. Proto-oncogenes overly expressed, leading to uncontrolled cell division.

    2. Tumor suppressor genes not effectively expressed.

  • Consequence of malfunction:

    • Cells enter S phase without checks, leading to mutations and tumor formation.

Role of P53 Protein

  • P53 Protein Functions:

    1. Check for DNA damage at G1 checkpoint.

    2. Repair damaged DNA.

    3. Arrest cell cycle at G1 until repair is complete.

    4. Trigger apoptosis if damage is irreparable.

Cancerous Changes

  • Defective P53 associated with many cancers.

  • Cancer mechanisms:

    1. Cells with DNA damage replicate uncontrollably.

    2. Release of growth factors promoting further cell division.

    3. Promote blood vessel growth to support tumor development.

Mutations and Their Triggers

  • Sources of Mutations:

    • Mistakes during DNA replication that may become permanent.

    • External damage from mutagens (UV radiation, toxins, etc.).

  • Example of a Mutagen:

    • UV light leading to thymine dimers.

Understanding Tumors

  • Tumors

    • Masses of cells dividing uncontrollably due to gene expression defects.

  • Types of Tumors:

    • Benign Tumors: Localized and do not spread.

    • Malignant Tumors: Can migrate (metastasize) and cause cancer.

Contrasting Benign and Malignant Tumors

  • Characteristics:

    • Benign: Well-differentiated, unspread.

    • Malignant: Poorly differentiated, capable of metastasis.

  • Mutations in control proteins lead to tumor distinction.

Cancer Treatment Approaches

  1. Immunotherapy: Train immune system to attack cancer cells.

  2. Angiogenesis Inhibitors: Cut off blood supply to tumors.

  3. Targeted Drug Delivery: Chemotherapy limited to cancer cells, minimizing side effects.

  4. Surgery: Remove tumors before metastasis.

  5. Radiation Therapy: Destroy tumor cells and adjacent tissues.

Key Concepts Summary

  • The cell cycle requires regulation for proper cell division.

  • Checkpoints are crucial in regulating progress and preventing tumor formation.