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Concept
Tumor suppressor gene
Summary
A tumor suppressor gene (TSG), or anti-oncogene, is a gene that regulates a cell during cell division and replication. If the cell grows uncontrollably, it will result in cancer. When a tumor suppressor gene is mutated, it results in a loss or reduction in its function. In combination with other genetic mutations, this could allow the cell to grow abnormally. The loss of function for these genes may be even more significant in the development of human cancers, compared to the activation of oncogenes.
TSGs can be grouped into the following categories: caretaker genes, gatekeeper genes, and more recently landscaper genes. Caretaker genes ensure stability of the genome via DNA repair and subsequently when mutated allow mutations to accumulate. Meanwhile, gatekeeper genes directly regulate cell growth by either inhibiting cell cycle progression or inducing apoptosis. Lastly landscaper genes regulate growth by contributing to the surrounding environment, when mutated can cause an environment that promotes unregulated proliferation. The classification schemes are evolving as medical advances are being made from fields including molecular biology, genetics, and epigenetics.
The discovery of oncogenes and their ability to deregulate cellular processes related to cell proliferation and development appeared first in the literature as opposed to the idea of tumor suppressor genes. However, the idea of genetic mutation leading to increased tumor growth gave way to another possible genetic idea of genes playing a role in decreasing cellular growth and development of cells. This idea was not solidified until experiments by Henry Harris were conducted with somatic cell hybridization in 1969.
Within Harris's experiments, tumor cells were fused with normal somatic cells to make hybrid cells. Each cell had chromosomes from both parents and upon growth, a majority of these hybrid cells did not have the capability of developing tumors within animals.
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