Cancer and Cell Division

Introduction to Cancer and the Cell Cycle

Cancer is fundamentally a disease of the cell cycle, arising when mutations accumulate in genes that regulate cell division. These mutations disrupt normal cell cycle control, leading to uncontrolled cell proliferation.

• Tumor suppressor genes: Genes such as p53 and BRCA1/BRCA2 that pause the cell cycle or initiate apoptosis.

• Proto-oncogenes: Genes like ras that promote cell cycle progression; when mutated, they become oncogenes and drive excessive cell division.

• DNA repair genes: Maintain genome integrity by repairing DNA damage.

Mutations and Their Sources

Mutations are changes in the DNA sequence and are the primary source of genetic errors leading to cancer.

• DNA replication errors: Mistakes during DNA synthesis.

• Non-disjunction: Failure of chromosomes to separate properly during mitosis or meiosis.

• Exposure to mutagens: Environmental agents such as radiation or chemicals that damage DNA.

Cell Division: Mitosis and Meiosis

Why Do Cells Divide?

Cell division is essential for growth, development, cell replacement, and wound healing.

• Growth and development: Formation of multicellular organisms from a single cell.

• Cell replacement: Replacement of dying cells to maintain tissue health.

• Wound healing: Repair of damaged tissues.

• Asexual reproduction: Some organisms reproduce by mitosis (e.g., hydra).

Mechanisms of Cell Division

Cells do not simply split in half; they must distribute a complete set of genetic material to each daughter cell.

• Genome size: Varies among organisms (e.g., prokaryotes: 2 million bp, humans: 3 billion bp).

• Eukaryotic chromosomes: Highly organized structures that ensure accurate distribution of genetic material.

Karyotype Preparation

Karyotyping is used to visualize chromosomes and detect abnormalities.

• G-banding: Staining technique to identify individual chromosomes.

• Human karyotype: Shows the complete set of chromosomes in a cell.

The Cell Cycle

Phases of the Cell Cycle

The cell cycle consists of two main phases:

• Interphase: Includes G1 (first gap), S (DNA synthesis), and G2 (second gap) phases. Cells grow, replicate DNA, and prepare for division.

• M phase (mitosis): Nuclear division followed by cytokinesis.

Interphase Details

• S phase: DNA replication occurs.

• G1 and G2 phases: Cell growth, organelle replication, and preparation for division.

• Duration: Typical cell cycle lasts about 24 hours.

Mitosis: Steps and Mechanisms

Mitosis is divided into several subphases:

• Prophase: Chromosomes condense, spindle apparatus forms.

• Prometaphase: Nuclear envelope breaks down, microtubules attach to kinetochores.

• Metaphase: Chromosomes align at the cell's equator.

• Anaphase: Sister chromatids separate and move to opposite poles.

• Telophase: Nuclear envelope reforms, chromosomes decondense.

• Cytokinesis: Division of cytoplasm and organelles.

Cytokinesis in Different Cell Types

• Plants: Vesicles form a cell plate.

• Animals, fungi, slime molds: Actin-myosin ring forms a cleavage furrow.

• Bacteria: Divide by binary fission, not cytokinesis.

Control of the Cell Cycle

Internal and External Controls

Cell cycle regulation is achieved through internal and external mechanisms.

• Internal controls: Cyclins, protein kinases, proto-oncogenes, tumor suppressors.

• External controls: Growth factors, hormones, density-dependent inhibition, anchorage dependence.

Cell-Cycle Checkpoints

There are three main checkpoints:

• G1 checkpoint: Ensures cell size, nutrients, and DNA integrity.

• G2 checkpoint: Ensures DNA replication is complete and undamaged.

• M-phase checkpoint: Ensures chromosomes are properly attached and segregated.

Cancer: Out-of-Control Cell Division

Genetic Basis of Cancer

Cancer arises from mutations in genes that regulate cell division and DNA repair.

• Multi-hit hypothesis: Multiple mutations are required for cancer development.

• Oncogenes: Mutated proto-oncogenes that promote cell division.

• Tumor suppressor genes: Loss of function leads to uncontrolled division.

• DNA repair genes: Defects increase mutation rates.

Properties of Cancer Cells

• Malignant tumors: Invasive, can metastasize (spread to other tissues).

• Benign tumors: Non-invasive, do not spread.

Key Genes in Cancer

• Proto-oncogenes (e.g., Ras): Promote cell division; mutations lead to constant activation.

• Tumor suppressors (e.g., p53, BRCA1/BRCA2): Inhibit cell division or repair DNA; mutations inactivate these functions.

• Apoptosis genes: Regulate programmed cell death.

• DNA repair genes: Maintain genome stability.

Cell Cycle Checkpoints and Cancer

• p53 protein: Pauses cell cycle, activates DNA repair, or initiates apoptosis if damage is irreparable.

• BRCA1/BRCA2: Involved in DNA repair, especially double-stranded breaks.

External Control and Cancer Therapy

External Controls and Cancer Cell Behavior

• Normal cells: Exhibit anchorage dependence and density-dependent inhibition.

• Cancer cells: Escape these controls, leading to uncontrolled growth.

Cancer Treatments

• Chemotherapy: Uses drugs to interfere with cell division (e.g., spindle formation, DNA replication).

• Radiation therapy: Uses high-energy beams to damage DNA and trigger apoptosis.

• Immunotherapies: New approaches targeting cancer cells via the immune system.

Prevention and Lifestyle

• Mutagens: Cancer-causing agents (e.g., X-rays, UV radiation, tobacco).

• Healthy lifestyle: Avoiding carcinogens, eating fiber and antioxidants, regular checkups.

Summary Table: Cell Cycle and Cancer

Comparison of Key Genes and Their Roles

Key Equations

• Genome size: $2 \times 10^6$ bp (prokaryote), $1.5 \times 10^8$ bp (Drosophila), $3 \times 10^9$ bp (human)

• Chromosome number after nondisjunction: $2n+1$ or $2n-1$

Additional info:

• Some details about BRCA1/BRCA2 and immunoprecipitation were inferred for completeness.

• Tables and diagrams were recreated based on academic context.