Tumor suppressor genes play a role in preventing proliferation of cancer

As the name suggests, tumor-suppressor genes prevent cancerous growth. When it becomes inactivated, it becomes more likely that cancer will arise (618),
Retinoblastoma is caused by a "two-hit" model of tumor-suppressor gene deactivation. People with the hereditary form only have 1 functional gene from parents; they only need 1 additional mutation in the other copy of the tumor suppressor gene to develop the disease. Since the retina contains more than 1 million cells, it is relatively likely that a mutation may occur at an early age (618).
- The mutated gene is called rb; it's located on long arm of chromosome 13.
- The rb protein inhibits E2F, which prevents the cell cycle from progressing. When rb goes offline, E2F is not turned off (618-619).

The p53 gene

Most commonly altered in all human cancers (619).
Role of p53 is to determine if a cell has incurred DNA damage; if damage is detected, p53 can promote 3 types of pathways aimed at preventing the proliferation of the damaged cell (619):
1. Repair the DNA, which may prevent the accumulation of mutations that activate oncogenes or inactivate tumor-suppressor genes.
2. Arrest the cell cycle. This gives the cell more time to repair its DNA and prevents the production of mutated daughter cells.
3. Stimulates apoptosis.
Expression of p53 caused by formation of damaged DNA. Specifically, the inducing signal for p53 is a double-stranded DNA break (619).
- Functions as a transcription factor; it can activate genes that promote DNA repair, arrest the cell cycle, and promote apoptosis.
- It also appears to act a negative regulator by interacting with general transcription factors, which may prevent the cell from dividing.

Tumor suppressor genes can no longer inhibit cancer when function is lost

The general function of tumor-suppressor genes are either to negatively regulate cell division or negatively regulate genes that maintain genome integrity (620).
Some tumor-suppressor genes encode proteins that have direct effects on the regulation of cell division, such as the rb gene. When these go offline, it has a direct impact on the abnormal cell division rates seen in cancer cells (620).
Some tumor-suppressor genes play a role in genome maintenance, which refers to the cellular mechanisms that either prevent mutations from happening and/or prevent mutant cells from surviving. These can either be checkpoint proteins and DNA repair enzymes (620).
- Checkpoint proteins detect abnormalities, such as DNA breaks and improperly segregated chromosomes.
  - Cyclins and cyclin-dependent protein kinases are responsible for advancing a cell through the 4 phases of the cell cycle.
  - G1 and G2 checkpoints involve sensing of the DNA has incurred damage. If it has, checkpoint proteins such as p53 can prevent the formation of the cyclin/cyclin-dependent protein kinase complexes from forming, which stops the progression of the cell cycle.
  - If checkpoint proteins are lost, it becomes more likely that undesireable genetic changes will occur and cause cancerous growth.
- DNA repair enzymes. The loss of these enzymes makes it more likely for a cell to accumulate mutations that create an oncogene and/or eliminate the function of a tumor-suppressor gene.

For info on how tumor-suppressor genes are deactivated, visit page 621.

For info on DNA microarrays and tumor classification, visit page 623-624,

For info on inherited forms of cancer, visit page 624-625

	Erstellt von Olivia McRitchie vor etwa 6 Jahre

NCLEX Biology (Genetics) Notiz am Ch 22: Medical Genetics and Cancer, erstellt von Olivia McRitchie am 02/05/2018.