BIOMED SCIE Lecture 25 cancer 2

• Oncogenes


  Arising from mutation or overexpression of proto-oncogenes. Oncogenes can also be introduced by a virus.
• Tumor suppressor genes


  Slow cell division to allow DNA repair
• DNA repair genes


  Mutations occur in these genes and cause cancer
• How proto-oncogenes transform into oncogenes

  1. Mutations altering the protein

  2. Increased or inappropriate expression
• Proto-oncogenes


  • Genes that code for proteins that support cell growth, the cell cycle, or prevent normal cell death (e.g., growth factors, regulatory GTPases, transcription factors, etc.)
• Oncogene example


  • Ras GTPase gene (ras) mutates, found in approximately 20% of human cancers
• Growth factors


  Molecules like fibroblast growth factor (FGF), nerve growth factor (NGF), and epidermal growth factor (EGF) that cells require to proliferate
• How growth factor signaling can lead to cancer


  1. Growth factors bind to cell surface receptors

  2. Initiates internal molecular changes

  3. Activates cell cycle and mitosis genes by transcription factors

  4. Abnormal proteins can relay growth factor receptor signals, leading to hyperactive signaling without growth factors
• Tumor suppressor genes


  Genes like p53 that detect DNA damage, halt the cell cycle for repair or promote apoptosis if the damage is irreparable
• Over half of all cancers involve mutations in p53
• Virus-induced cancers


  Viruses can carry oncogenes that transform infected cells into cancerous ones
• Viruses that can cause cancer

  • Rous sarcoma virus, Epstein-Barr virus, Hepatitis B, Human papillomavirus
• Some viruses can cause secondary effects that contribute to cancer development, such as HIV impairing the immune system's cancer surveillance
• Inherited cancer-contributing mutations


  Mutations in genes like BRCA1 and BRCA2 that encode proteins that repair DNA and act as tumor suppressors
• Mutations in BRCA genes increase breast cancer risk by up to 60%
• Chromosomal abnormalities


  Some cancers arise from acquired chromosomal abnormalities, like the Philadelphia Chromosome, leading to abnormal fusion genes associated with leukemia
• Hormones and cancer


  Hormones can stimulate cell growth in target tissues and contribute to cancer proliferation (e.g., estrogen in breast cancer). Obesity-related hormonal changes can also impact cancer risk.
• Apoptosis


  Normal cells undergo programmed cell death triggered by various signals. Cancer cells often evade apoptosis by overexpressing anti-apoptotic proteins like bcl-2.
• Immortality and cell division


  Cancer cells can achieve immortality by avoiding normal cell cycle controls and apoptosis. Telomerase activity, which extends telomeres at chromosome ends, allows cancer cells (and stem cells) to replicate indefinitely.
• Cancer cells used in research

  • HeLa cells from Henrietta Lacks' cervical cancer, have been crucial in laboratory research due to their immortal nature. They have contributed significantly to medical discoveries, with over 20 tons of HeLa cells used in various studies and patents.