Tumor suppressor gene

Genes that protect a cell from one step on the path to cancer

Tumor suppressor genes are a class of genes that play a critical role in regulating the cell cycle, repairing DNA, and ensuring the stability of a cell's genome. When these genes are mutated or inactivated, cells can grow uncontrollably, leading to the development of cancer.

Function

Tumor suppressor genes are essential for maintaining normal cellular functions. They can be categorized into several types based on their roles:

• Gatekeepers: These genes directly regulate cell growth by controlling the cell cycle and promoting apoptosis (programmed cell death). Examples include the retinoblastoma protein (pRB) and p53.

• Caretakers: These genes are involved in maintaining genomic integrity by repairing DNA damage. Mutations in caretaker genes can lead to increased mutation rates in other genes, including gatekeepers. Examples include BRCA1 and BRCA2.

• Landscapers: These genes influence the surrounding cellular environment, which can affect tumor development. They are less well-defined compared to gatekeepers and caretakers.

Mechanism

Tumor suppressor genes typically require both alleles to be inactivated for a loss of function, a concept known as the "two-hit hypothesis" proposed by Alfred Knudson. This hypothesis suggests that both copies of a tumor suppressor gene must be mutated for cancer to develop.

Illustration of the two-hit hypothesis.

Examples

• p53: Often referred to as the "guardian of the genome," p53 is a transcription factor that regulates the cell cycle and induces apoptosis in response to DNA damage.

• RB1: The retinoblastoma protein is crucial for controlling the cell cycle by inhibiting the transition from the G1 phase to the S phase.

• APC: The adenomatous polyposis coli protein is involved in the Wnt signaling pathway and helps regulate cell growth and adhesion.

Role in Cancer

Mutations in tumor suppressor genes are a common feature in many types of cancer. For instance, mutations in the p53 gene are found in approximately 50% of all human cancers. The loss of function in these genes removes critical checks on cell division and DNA repair, allowing for the accumulation of additional mutations that drive cancer progression.

Diagram of the cell cycle, highlighting the role of tumor suppressor genes in regulating cell division.

Models of Tumor Suppression

Several models have been proposed to explain how tumor suppressor genes function to prevent cancer:

• Oncogene-induced senescence: Tumor suppressor genes can induce a permanent state of cell cycle arrest in response to oncogenic signals.

• Apoptosis induction: In response to severe DNA damage, tumor suppressor genes can trigger apoptosis to eliminate potentially cancerous cells.

Different models of tumor suppression.

Related pages

• Oncogene
• Cell cycle
• Apoptosis
• DNA repair