Genome Regulation: Cancer and Cell Cycle Control

Cancer and Gene Regulation

• Cancer results from genetic changes that affect cell cycle control, involving the same gene regulation systems active during embryonic development.

Types of Genes Associated with Cancer

• Cancer can be caused by mutations in genes regulating cell growth and division.
• Tumor viruses can cause cancer in animals, including humans.
• Oncogenes are cancer-causing genes, while proto-oncogenes are their normal cellular counterparts responsible for normal cell growth and division.
• Conversion of a proto-oncogene to an oncogene can lead to abnormal stimulation of the cell cycle.

Proto-oncogene Conversion to Oncogenes

• Proto-oncogenes can be converted to oncogenes through:
  • Movement of DNA within the genome, resulting in increased transcription near an active promoter.
  • Amplification of a proto-oncogene, increasing the number of gene copies.
  • Point mutations in the proto-oncogene or its control elements, causing increased gene expression.

Tumor-Suppressor Genes

• Tumor-suppressor genes help prevent uncontrolled cell growth.
• Mutations decreasing protein products of tumor-suppressor genes may contribute to cancer onset.
• Tumor-suppressor proteins:
  • Repair damaged DNA.
  • Control cell adhesion.
  • Inhibit the cell cycle in the cell-signaling pathway.

Interference with Normal Cell-Signaling Pathways

• Mutations in the ras proto-oncogene and p53 tumor-suppressor gene are common in human cancers.
• Ras gene mutations can lead to production of a hyperactive Ras protein, increasing cell division.
• Suppression of the cell cycle is critical in cases of DNA damage; p53 prevents a cell from passing on mutations.