Cell and cancer

• Correct regulation of cell division is important
• Cell cycle checkpoints

  Points in the cell cycle where the cell checks if conditions are right to proceed to the next phase
• Regulation of the cell cycle

  1. Cyclins and cyclin-dependent kinases regulate the cell cycle

  2. Internal regulatory complexes such as the Maturation Promotion Factor (MPF) regulate the cell cycle
• 1 in 2 people will in their lifetime develop cancer
• Cancer is becoming more common in the UK
• Mortality rate for cancer is decreasing
• Cancer has recently overtaken heart disease as the leading cause of death in the UK
• Better treatment for heart disease and an aging population are reasons why cancer has overtaken heart disease as the leading cause of death
• Deaths from different forms of cancer in the UK; 2010


  • Lung cancer - most common cancer (both sexes)
  • Prostate cancer - second biggest killer in men
  • Breast cancer - second biggest killer in women
• Cancer


  A serious disease that is caused when cells in the body grow in a way that is uncontrolled and not normal, killing normal cells and often causing death
• Cancer is a complex family of diseases, with as many forms as there are types of cell in the body
• Types of cancer

  • Carcinoma
  • Sarcoma
  • Myeloma
  • Lymphoma
  • Leukemia
• Normal cells

  • Anchorage dependent growth
  • Density dependent growth
• Cancerous cells


  • No anchorage dependence
  • No density dependence
• Immortality

  Normal diploid cells have limited life expectancy in culture, while cancerous cells can divide indefinitely
• Cancerous cells are able to maintain telomere length through telomerase, unlike normal cells
• Reduced reliance on growth factors


  Cancerous cells require less external growth factors to progress through the cell cycle
• Increased production of growth factors

  Cancerous cells may overproduce their own growth factors to promote growth
• Changes in cell membrane structure and function

  The cell surface and plasma membrane of cancerous cells differ from normal cells, affecting communication, movement, adherence, and immune recognition
• Basic stages of cancer disease progression

  1. Initiation

  2. Clonal expansion

  3. Primary tumour

  4. Secondary mutations

  5. Malignancy

  6. Invasion

  7. Metastasis
• Characteristics of malignant tumour cells

  • Excessive proliferation
  • Unusual number of chromosomes (aneuploidy)
  • Deranged metabolism
  • Reduced attachments to neighbouring cells
  • Invasive phenotype
  • Proliferate in other parts of the body - METASTASIS
• Carcinogens can cause DNA mutations that lead to cancer
• Examples of carcinogens

  • Cigarette smoke
  • Sunlight - UV radiation
  • Viruses - e.g. human papillomavirus (HPV)
• Proto-oncogene

  Normal gene regulating cell division
• Oncogene


  Proto-oncogene that has been mutated, leading to excess growth-stimulating activity
• How proto-oncogenes become oncogenes

  1. New promoter means gene transcribed more efficiently - more protein

  2. Gene replicated - more total protein

  3. Mutation in existing promoter - more efficient transcription

  4. Changes the protein itself - more growth promoting
• Identifying oncogenes

  1. Extract DNA from human tumor cells - contains mutated oncogene

  2. Introduce tumor DNA into mouse cells (3T3) - cells with oncogene will proliferate and form dense foci

  3. Extract DNA from foci - now contains the human oncogene

  4. Fragment DNA and introduce into bacterial virus (phage library)

  5. Detect human DNA in phages using Alu sequence probe
• Signaling pathways involving oncogenes

  1. Growth factor binds to receptor, causing autophosphorylation

  2. Phosphorylated receptor activates Ras, a small G protein

  3. Activated Ras signals to a MAPK cascade

  4. MAPK cascade ends by phosphorylating a transcription factor in the nucleus, enhancing expression of cell cycle genes like cyclins
• Ras oncogene


  • Differs from proto-Ras by a single nucleotide, causing it to remain permanently bound to GTP and active
  • Stimulatory signal to nucleus never switched off, leading to excessive cyclin production and uncontrollable growth
  • Explains why cancer cells don't require external growth factors
• Mutations in tumor suppressor genes also contribute to cancer development
• how to classify a carcinoma?

  Cancers arising from epithelial cells
• How to classify a sarcoma?

  Cancers of connective and supportive tissues
• What is the classification of myeloma?

  cancers of the plasma cells of the bone marrow - antibody producing cells - secondary infections
• Lymphoma: solid tumour of the lymphatic system, lymph glands, lymph nodes or in organs - tonsils, spleen, thymus -formed from maturing WBCs
• Leukemia: blood cancers - more specifically precursor blood cells in bone marrow
• mixed classification: cancers originating in germ cell and stem cell
• Factor contributing to the abnormal proliferation of cancerous cells:

  1. immortality
  2. reduced reliance on growth factors produced by other cells
  3. Increased production of growth factor
  4. changes in cell membrane structure and function
• initiation: single cell undergoes a single mutation confers a growth advantage which causes it to lose some of its growth control
• Clonal expansion: proliferation begins - mutated cell divides quicker than surrounding cells to form a cluster of clones disease is monoclonal
• Primary tumour: The cancer remains in situ. Tumour benign - not invaded surrounding tissue surgery possible