LESSON 5 Cell Cycle and Tumor Formation: Structure, Regulation, and Cancer Development

Cell Cycle and Tumor Formation

Introduction

The cell cycle is a fundamental process in biology, governing how cells grow, replicate their DNA, and divide. Proper regulation of the cell cycle is essential for growth, development, and tissue repair. Disruption of cell cycle control can lead to uncontrolled cell proliferation and tumor formation, which underlies cancer development.

Organization of DNA in the Cell

Chromatin Structure

• Chromatin is the complex of DNA and proteins (mainly histones) found in the nucleus of eukaryotic cells.

• DNA wraps around histone proteins to form nucleosomes, which further coil and fold to form higher-order structures.

• Chromatin exists in two main forms: euchromatin (less condensed, transcriptionally active) and heterochromatin (highly condensed, transcriptionally inactive).

Chromosomes and Chromatids

• Chromosomes are highly condensed structures of chromatin visible during cell division.

• Each duplicated chromosome consists of two sister chromatids joined at a region called the centromere.

• Somatic cells are diploid (2N), containing two sets of chromosomes, while gametes are haploid (N).

The Cell Cycle: Phases and Regulation

Phases of the Cell Cycle

• Interphase: The cell grows and DNA is replicated. It consists of three subphases:

  • G1 phase: Cell growth and normal functions

  • S phase: DNA synthesis (replication)

  • G2 phase: Preparation for mitosis

• M phase (Mitotic phase): Includes mitosis (division of the nucleus) and cytokinesis (division of the cytoplasm).

Mitosis: Stages and Key Structures

• Prophase: Chromatin condenses into visible chromosomes; mitotic spindle begins to form.

• Prometaphase: Nuclear envelope breaks down; spindle fibers attach to kinetochores.

• Metaphase: Chromosomes align at the metaphase plate.

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

• Telophase: Nuclear envelopes reform; chromosomes decondense.

• Cytokinesis: Cytoplasm divides, forming two daughter cells.

Mitotic Spindle and Microtubules

• The mitotic spindle is a structure made of microtubules that segregates chromosomes during mitosis.

• Microtubules are dynamic polymers of α- and β-tubulin that grow (polymerize) and shrink (depolymerize) as needed.

• Kinetochores are protein complexes on chromosomes where spindle fibers attach.

Cytokinesis

• In animal cells, cytokinesis occurs via a cleavage furrow formed by a contractile ring of actin microfilaments and myosin.

Cell Renewal and Division in Human Tissues

Cell Turnover Rates

Different tissues in the human body have varying rates of cell renewal, reflecting their function and exposure to damage.

Cell Type	Turnover Time
Small intestine epithelium	2-4 days
Stomach	2-9 days
Blood Neutrophils	1-5 days
Blood platelets	10 days
Skin epidermal cells	20-30 days
Red blood cells (RBCs)	~120 days
Oocytes (female gametes)	Lifetime
Cardiomyocytes	0.5-1% per year

Regulation of the Cell Cycle

Cell Cycle Control System

• Progression through the cell cycle is regulated by internal and external signals.

• Internal signals: Cyclins and cyclin-dependent kinases (Cdks) regulate transitions between phases.

• External signals:

  • Growth factors: Chemical signals that stimulate cell division.

  • Anchorage dependence: Cells must be attached to a substrate to divide.

  • Density-dependent inhibition: Cells stop dividing when they become too crowded.

Loss of Cell Cycle Control and Tumor Formation

Transformation and Cancer

• Transformation is the process by which a normal cell becomes a tumor cell, often due to mutations in genes controlling cell growth and division.

• Key gene groups involved:

  • Proto-oncogenes: Normal genes that promote cell growth and division. When mutated, they become oncogenes that drive uncontrolled proliferation (e.g., ras).

  • Tumor-suppressor genes: Inhibit cell division, repair DNA, and promote apoptosis. Loss of function (e.g., p53) removes these brakes on the cell cycle.

Multistep Model of Cancer Development

• Cancer typically arises from the accumulation of multiple mutations over time, affecting both proto-oncogenes and tumor-suppressor genes.

• One mutation is usually insufficient; several genetic changes are required for malignant transformation.

Benign vs. Malignant Tumors

• Benign tumors remain localized and do not invade other tissues.

• Malignant tumors invade surrounding tissues and can spread (metastasize) via blood or lymphatic vessels, resulting in cancer.

Summary Table: Key Terms and Concepts

Term	Definition
Chromatin	DNA-protein complex in the nucleus
Chromosome	Condensed chromatin visible during cell division
Sister chromatids	Identical copies of a chromosome joined at the centromere
Interphase	Cell growth and DNA replication phase
Mitosis	Nuclear division phase
Cytokinesis	Cytoplasmic division phase
Proto-oncogene	Gene promoting normal cell growth
Oncogene	Mutated proto-oncogene causing cancer
Tumor-suppressor gene	Gene inhibiting cell division

Key Equations and Concepts

• DNA replication during S phase: $\text{DNA}_{\text{after S phase}} = 2 \times \text{DNA}_{\text{before S phase}}$

• Cell division produces two genetically identical daughter cells (except in meiosis).

Example: Skin Healing

When the skin is injured, cell division in the basal layer of the epidermis increases to replace lost or damaged cells, demonstrating the importance of regulated cell proliferation in tissue repair.

Additional info:

• Mutations in ras (a proto-oncogene) can lead to constant cell division signals, while loss of p53 (a tumor-suppressor gene) impairs DNA repair and apoptosis, both contributing to cancer.