Suppose that you have cancer cell line X was treated with drug Y to increase the expression levels of protein Z which is a tumor suppressor gene.
Explain How can you study protein Z in these cells?
Explain how can you study protein Z components?
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A tumor suppressor gene, 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
Tumor suppressor genes (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 proteins encoded by most tumor suppressor genes inhibit cell proliferation or survival. Inactivation of tumor suppressor genes therefore leads to tumor development by eliminating negative regulatory proteins. In most cases, tumor suppressor proteins inhibit the same cell regulatory pathways that are stimulated by the products of oncogenes.While tumor suppressor genes have the same main function, they have various mechanisms of action, that their transcribed products perform, which include the following:
- Intracellular proteins, that control gene expression of a specific stage of the cell cycle. If these genes are not expressed, the cell cycle does not continue, effectively inhibiting cell division. (e.g., pRB and p16)
- Receptors or signal transducers for secreted hormones or developmental signals that inhibit cell proliferation (e.g., transforming growth factor (TGF)-β and adenomatous polyposis coli(APC)).
- Checkpoint-control proteins that trigger cell cycle arrest in response to DNA damage or chromosomal defects (e.g., breast cancer type 1 susceptibility protein (BRCA1), p16, and p14).
- Proteins that induce apoptosis. If damage cannot be repaired, the cell initiates programmed cell death to remove the threat it poses to the organism as a whole. (e.g., p53).
- Cell adhesion. Some proteins involved in cell adhesion prevent tumor cells from dispersing, block loss of contact inhibition, and inhibit metastasis. These proteins are known as metastasis suppressors. (e.g., CADM1)
- Proteins involved in repairing mistakes in DNA. Caretaker genes encode proteins that function in repairing mutations in the genome, preventing cells from replicating with mutations. Furthermore, increased mutation rate from decreased DNA repair leads to increased inactivation of other tumor suppressors and activation of oncogenes.(e.g., p53 and DNA mismatch repair protein 2(MSH2)).
- Certain genes can also act as tumor suppressors and oncogenes. Dubbed Proto-oncogenes with Tumor suppressor function, these genes act as “double agents” that both positively and negatively regulate transcription. (e.g., NOTCH receptors,
Tumor suppressor genes make proteins that regulate the growth of cells, and they play an important role in preventing the development of cancer cells.
When tumor suppressor genes are altered or inactivated due to a mutation (either one that is present at birth or one that occurs later in life), they make proteins that are less effective at controlling cell growth and/or repair. The result is unchecked growth of damaged or abnormal cells, which leads to uncontrolled growth and the development of cancerous tumors.
Tumor suppressor genes are also known as antioncogenes or loss-of-function genes.
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