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  • Writer's pictureDr Edin Hamzić

What Are Proto-Oncogenes and Oncogenes?

Updated: Oct 22, 2023

Alterations in critical regulatory genes that control cell proliferation, differentiation, and survival lead to the onset of cancer.

Scientific studies of tumor viruses initially revealed that specific genes now known as oncogenes could induce cancer, and these were the first insights into the molecular basis of carcinogenesis. These oncogenes were known as viral oncogenes.

Most human cancers are not induced by viruses and arise from other causes, such as radiation, chemical carcinogens, and errors that occur during DNA replication. So, the following critical step was the identification of cellular oncogenes. Cellular oncogenes are involved in the development of non-virus-induced cancers.

What Is a Proto-oncogene? What Do Proto-Oncogenes Normally Do?

A proto-oncogene is a normal gene in the human genome that, once it mutates, becomes an oncogene. Oncogenes are cancer-causing genes. Proto-oncogenes usually perform essential cellular functions in the human body, such as the cell’s growth, proliferation, and survival.

What Is the Difference Between a Proto-Oncogene and an Oncogene?

Proto-oncogenes are normal cell genes that are, by nature, cell regulatory genes, in most cases encoding proteins that function in the signal transduction pathways controlling cell proliferation (some of those genes are, for example, NRAS, KRAS).

Conversely, the oncogenes are abnormally expressed or mutated forms of the corresponding proto-oncogenes. Consequently, these oncogenes lead to abnormal cell proliferation and tumor development.

To summarize, an oncogene is a mutated version of the corresponding proto-oncogene.

What Is a Cellular Oncogene?

Cellular oncogenes originate from proto-oncogenes due to mutation, transcriptional activation, or other genetic alterations.

What Is a Viral Oncogene?

An oncogenic virus is any virus (DNA or RNA) that causes cancer by affecting the host through adding genes or enhancing the activity of already existing genes.

How Does Proto-Oncogene Become Oncogene? What Are Three Mechanisms for Converting a Proto-Oncogene to an Oncogene?

Genetic events such as mutations, gene fusions, and overexpression may lead to cancer or malfunctioning genes. Any adverse circumstances, such as mutations, gene fusions, and overexpression, may lead to cancer or malfunctioning genes. Three mechanisms for converting a proto-oncogene to an oncogene are mutation, chromosomal rearrangement, and gene amplification.

What Type of Proteins Are Encoded by Proto-Oncogenes?

Generally, those are genes involved in biological function for cell signaling, cell development, cell differentiation, cell proliferation, apoptosis, cell survival, transcription factors, and others. Proteins are involved in biological functions for signaling, development, cell differentiation, proliferation, apoptosis, survival, transcription factors, etc.

What Do Oncogenes Cause? Why Are Proto-Oncogenes Dominant?

Oncogenes cause uncontrollable replication of cells that can lead to cancer. They are dominant because it is usually one mutation (in pair of genes) that can lead to developing cancer.

What Are Proto-Oncogene and Tumor Suppressor Genes?

As mentioned above, proto-oncogenes usually perform critical functions in the human body. For example, proto-oncogenes regulate or control cell growth, proliferation, and survival. On the other hand, tumor-suppressor genes or anti-oncogenes perform a control cell division and replication by suppressing those processes. Inactivation (loss of function) of the tumor suppressor gene leads to cancer development.

What Are Some of the Oncogenes?

There is a long list of oncogenes, and I have already written several posts about some of the most important oncogenes ones, such as:

  1. The ALK gene. The ALK gene as an oncogene was initially described in lymphoma, but most ALK-positive cancers are non-small cell lung cancer. If interested, please check my blog post about the ALK gene.

  2. The EGFR gene. A wide range of cancers is associated with the EGFR gene. The EGFR mutations are found in lung adenocarcinoma, conventional glioblastoma multiforme, glioblastoma, colon adenocarcinoma, and non-small cell lung carcinoma. Please check my blog post here for a detailed overview of the EGFR gene.

  3. The BRAF gene. Cancers associated with the BRAF gene, similar to ones associated with the EGFR gene, are across different types of tissues. However, melanoma is the most common cancer associated with BRAF gene mutations. If interested, please check my blog post about the BRAF gene.

  4. The NRAS gene. Among others, the two main types of cancer associated with mutations in the NRAS gene are colon cancer and melanoma. So, if you are interested in reading more about the NRAS gene and its oncogenic effect, please check my article about the NRAS gene.

  5. The EZH2 gene. Another gene with oncogenic characteristics is the EZH2 gene associated with lymphoma, among other cancers. You can find my blog post about the EZH2 gene here.

  6. The KRAS gene. Mutations in the KRAS gene are found in roughly ~25% of tumors, making it one of the genes most commonly linked to cancer. You can find my blog post about the KRAS gene here.



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