The main difference between tumor suppressor genes and proto oncogenes is that the removal or inactivation of tumor suppressor genes causes cancers whereas the activation of the proto-oncogenes causes cancers. Furthermore, tumor suppressor genes suppress the cell division while proto-oncogenes activate the cell division.
Tumor suppressor genes and proto-oncogenes are the two major classes of genes that can cause cancers upon mutation.
Key Areas Covered
1. What are Tumor Suppressor Genes
– Definition, Facts, Loss of Function
2. What are Proto Oncogenes
– Definition, Facts, Gain of Function
3. What are the Similarities Between Tumor Suppressor Genes and Proto Oncogenes
– Outline of Common Features
4. What is the Difference Between Tumor Suppressor Genes and Proto Oncogenes
– Comparison of Key Differences
Key Terms
Antioncogenes, Cancer, Gain of Function, Loss of Function, Proto Oncogenes, Ras Gene, RB Gene, Tumor Suppressor Genes
What are Tumor Suppressor Genes
Tumor suppressor genes are a class of genes that produce proteins to inhibit cell division, repair DNA mistakes, and control the cell death. They are also called antioncogenes. The first tumor suppressor genes to be identified is the RB gene; its mutated form causes retinoblastoma. The RB gene helps in the regulation of the progression of cell cycle. There are five classes of proteins encoded by tumor suppressor genes.
Proteins Encoded by Tumor Suppressor Genes
- Intracellular proteins (e.g. p16 cyclin-kinase inhibitor) – Regulate or inhibit progression through a specific stage of the cell cycle
- Receptors for secreted hormones (e.g. tumor-derived growth factor β) – Inhibit cell proliferation
- Checkpoint-control proteins – Arrest the cell cycle if DNA is damaged or chromosomes are abnormal
- Proteins that promote apoptosis
- Enzymes that participate in DNA repair
Figure 1: Loss of Function of Tumor Suppressor Genes
The loss of function in tumor suppressor genes by a mutation causes increased cell division, which may cause cancers. Both alleles of the tumor suppressor gene have to be inactivated to promote the development of tumors. However, the inheritance of a single mutated allele of many tumor suppressor genes such as RB, APC, and BRCA1 can cause the development of a tumor. Mutated APC gene cause colon cancers while mutated BRC1 gene causes breast cancers. Deletions or point mutations are the main cause of mutations in tumor suppressor genes.
What are Proto Oncogenes
Proto-oncogenes are a class of genes that produce proteins to enhance cell division and prevent cell death. Ras gene is a proto-oncogene, which encodes an intracellular signal-transduction protein. The gain-of-function of the Ras gene produces excessive growth-promoting signals, which increases the cell division, leading to cancer development. The elevated amounts of gene products due to mutation cause excessive signals. The activated proto-oncogene is called an oncogene. Point mutations, gene amplification, and chromosomal translocations produce oncogenes.
Mutation of one proto-oncogene allele in the pair can cause cancers. Therefore, oncogenes exhibit an aggressive behavior.
Similarities Between Tumor Suppressor Genes and Proto Oncogenes
- Tumor suppressor genes and proto-oncogenes are two classes of genes that can cause cancers upon mutation.
- Mutations of both genes affect the rate of cell division.
Difference Between Tumor Suppressor Genes and Proto Oncogenes
Definition
Tumor suppressor genes refer to protective genes that help to control the cell growth while the proto-oncogenes refer to normal genes which, when altered by mutation, become oncogenes that can contribute to cancer.
Influence of the Mutation
Mutations alter the gene products of tumor suppressor genes that inhibit the progression of the cell cycle, causing the development of tumors while mutations alter the gene products of proto-oncogenes in such a way to increase their expression, which cause cancer by increasing cell division.
Influence on Cell Division
Tumor suppressor genes suppress cell division while proto-oncogenes activate cell division.
Cause Cancers
The inactivation of tumor suppressor genes causes cancers while the activation of proto-oncogenes causes cancers. Moreover, the inactivation of tumor suppressor genes is called the ‘loss of function’ while the activation of proto-oncogenes is called the ‘gain of function’.
Types of Mutations
Deletions or point mutations are the main cause of mutations in tumor suppressor genes while point mutations, gene amplification, and chromosomal translocations produce oncogenes.
Mutations Occur in
Mutations of tumor suppressor genes can occur in the somatic or germ-line cells while the mutations of the proto-oncogenes occur in the somatic tissue. Therefore, mutations in the tumor suppressor genes may be inherited while the mutations of the proto-oncogenes will not be inherited to the next generation.
Tissue Preference
Tumor suppressor genes exhibit a high tissue preference while proto-oncogenes exhibit low tissue preference.
Dominant/Recessive
Cancer development by tumor suppressor genes is recessive since both copies of alleles have to be mutated to develop cancer while cancer development by oncogenes is dominant since a mutation of a single copy can cause cancers. Therefore, tumor suppresser gene exhibit less aggressive behavior while oncogenes are more aggressive.
Examples
Some tumor suppressor genes are RB, APC, and BRCA1 while Ras gene, HER-2, BCR/ABL, EGFR, and VEGF are proto-oncogenes.
Types of Cancers Caused
Retinoblastoma, colon cancers, and breast cancers are some of the cancers caused by tumor suppressor genes while chronic myeloid leukemia, breast cancer, kidney cancer are some of the cancers caused by oncogenes.
Conclusion
The gene products of tumor suppressor genes inhibit the progression of the cell cycle. Therefore, they have to be inactivated in order to cause cancers. On the other hand, the gene products of proto-oncogenes activate cell division. Hence, activation of oncogenes increases these gene products, causing the development of cancers. Therefore, the main difference between tumor suppressor genes and proto oncogenes is the influence of the mutation.
Reference:
1. Lodish, Harvey. “Proto-Oncogenes and Tumor-Suppressor Genes.” Advances in Pediatrics., U.S. National Library of Medicine, 1 Jan. 1970, Available Here
Image Courtesy:
1. “Two hit malignant transformation with chromosome loss”By Wpeissner – Own work (CC BY-SA 3.0) via Commons Wikimedia
2. “Ch1-oncogene” By Philippe Hupé – Emmanuel Barillot, Laurence Calzone, Philippe Hupé, Jean-Philippe Vert, Andrei Zinovyev, Computational Systems Biology of Cancer Chapman & Hall/CRC Mathematical & Computational Biology , 2012 (CC BY-SA 3.0) via Commons Wikimedia
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