Question

Give two examples of tumour suppressor genes and two examples of oncogenes, describe their action, and indicate cancers in which they are inactivated.

Answer 1

Oncogenes are the genes occuring in the body in the inactive state called proto-oncogenes and are activated and converted to oncogenes. There are about 5 classes of oncogenes.

classI: These are protein kinase encoding genes like src, located in th eplasma membrane and exhibit the activity of tyrosine specific protein kinases.

Class II: These are GTP binding proteins like H - ras occuring in the plasma membrane and exhibit GTP binding and GTPase activities.

Class III: These are Growth factors encoding genes like sis and are derived from gene encoding platelet derived groeth factor (PDGF).

Class IV: The are nuclear protein encoding genes like myc, myb and fos and cause changes in nucleus.

Class V: These are hormone receptors like erb A and rel and are located in the cytoplasm and act like thyroid hormone receptor.

The tumor supressor genes are found in the cells that prevent the growth of cancerous cells. When these genes contain a defect or undergo mutations losing their function they fail to control the proliferation of cancerous cells and hence result in cancer. For example, the retinoblastoma genes (RB genes) induce tumor in the retina during childhood. The somatic mutation or heritable trait results in loss of function of RB gene causing tumor in the retina. It is associated with deletion of band 14 of human chromosome 13.

Protein 53 is another example of tumor supressor genes. P53 is a nuclear phosphoprotein,it was first discovered in SV40 transformed cells associated with T antigen. Increase in the amount of p53 protein leads to trnasformation of cells causing tumor.

Answer 2

Tumor suppressor gene is a gene that protects a cell from cancer by inhibiting the uncontrolled cell division. This gene functions by producing protein products that repressing the genes that are essential for the cell cycle to continue; some proteins couples the cell cycle to DNA damage, and some proteins activate apoptosis.

For example, pRb (Retinoblastoma protein), and p53; p53 is inactivated in colon cancers, and pRb is inactivated in retinoblastoma.

Oncogene is a gene that can cause cancer. A mutation is proto-oncogene can become an oncogene. This gene functions by having a mutation that increases a activity of proteins (enzyme) which is necessary for a cell to continue cell cycle, loss of regulation. These genes produce proteins that are required for uncontrolled DNA replication, and chromosomal translocation.

For example, Bcl-2, a gene that inhibits apoptosis, overexpression of this gene is responsible for B-cell cancers.

Ras genes, mutations in Ras gene leads to almost all types of cancers.