Oncogenes
I. INTRODUCTION
The gene that causes cancer is called an oncogene. Proto-oncogenes are genes that code for proteins. Once a proto-oncogene is mutated it becomes an oncogene. Oncogenes are genes that are over expressed, mutated, or genes that are deleted. The word ‘oncos’ is a Greek word that means tumor. When a proto-oncogene is mutated it becomes an oncogene and the oncogene causes mutated cells to multiply very excessively. Oncogenes make up a very broad category of cancer causing cells. Oncogenes change normal cells into cancerous cells when mutated or they exist at a high level. A mutation occurs in an oncogene when the DNA is not properly repaired. An oncogene consists of two genes. If one gene is mutated the mutation takes over and produces other mutated oncogenes (Author Unknown 1996; Author Unknown 2001B; Carbone and Minna 1993; Davis 1999; Weinberg 1996).
There are over twenty different oncogenes that cause cancer. Not all oncogenes cause cancer. Some oncogenes are responsible for coding of proteins, growth of cells, growth inhibition, transcription, and they are used as messengers. Others cause cancer by tumor production, and others are tumor suppressors (Nowell 1991).
Researchers have found that two oncogenes combine to turn normal cell into a cancerous cell. The two oncogenes that interact are ras and myc. If the ras gene mutates it sends a signal to the myc gene to produce cell growth. Oncogenes are not the only thing responsible for cancer. A gene that is inherited also causes cancer in adults. The role of this inherited gene is unclear (Parker 1999; Nowell 1991).
Genes are either dominant or recessive. The dominant genes cause the growth of tumors and are called the dominant genes or oncogenes. The recessive genes do not cause the growth of tumor, but they can be reversed when associated with cancer. The recessive genes are called antioncogenes. The ineffectiveness of oncogenes or tumor suppressors can cause the formation of tumors (Author Unknown 1995; Carbone and Minna 1993).
II. FORMATION
In a normal cell DNA causes the cell to produce certain amounts of proteins. If a normal cell comes in contact with radiation, some chemicals, and some drugs it can cause a normal strand of DNA to break apart. A breakage in the strand of DNA is likely to cause incorrect recombination. This is likely to form an oncogene. The oncogene makes abnormally large amounts of the protein it produces. The abnormal amounts of proteins cause the cell to become cancerous. The cancerous cell is a different shape than the normal cell. When the cancerous cells are formed they divide to form cells called daughter cells. The daughter cells that are formed possess the same oncogene that the parent cell possessed (Author Unknown 2001A).
Telemerase plays a role in the formation of cancer cells. Telemerase is present only in human cancer cells, and not in normal human cells. Research in mice has shown that telemerase is present all the time in their cells. Scientists feel that telemerase is involved in the formation of cancerous cells, but the role it plays is unclear (Author Unknown 1999).
III. HISTORY
The word oncogene is a word that was derived from the Greek word oncos. The first oncogene to be discovered was the v-src oncogene. In 1976 a research group found the matching proto-oncogene for v-src. It was named c-src. This oncogene was named after the virus it was first found in. The virus was the Rous sarcoma virus. Over a dozen proto-oncogenes and over twenty oncogenes have been discovered. The first tumor suppressor gene to be discovered was rb (Author Unknown 1995; Nowell 1991).
IV. DISCOVERY
Cells replicate very fast. Once a cell has been mutated it carries that mutation and passes it on to any cell that it replicates. Certain substances such as dimethylsulfoxide caused mutated cells to replicate. When oncogenes and anti-oncogenes were first discovered they were called S and E genes. Two of the genes in a cell are the S gene and the E gene. The S gene is a suppression gene. The E gene is an expression gene. The E gene allows the spread of mutated cells. The S gene was later named the anti-oncogene. The E gene was later named the oncogene (Sachs 1986).
V. TYPES
Each type of oncogene causes a different type of cancer. Some oncogenes, for example the abl, cause leukemia. Ha-ras oncogenes cause tumors to form. Others such as fes and fgr effect the amount of a protein that is produced. Some oncogenes cause lung cancer, such as L-myc. And other oncogenes affect the binding of the DNA. Myc is an oncogene responsible for replication. Il3 and E2A are responsible for growth regulation. Oncogenes that are responsible for tumor suppression are p53, DCC, MCC, and Rb. The papilloma virus is caused by oncogenes E6 and E7 (Table 1) (Davis 1999, Nowell 1991).
Two of the most common oncogenes that form tumors are myc and ras. The ras gene sets on the replicator gene and keeps it in the on position. The myc and ras oncogenes cause cancer because the ras gene controls the myc gene. The myc gene controls the growth of the cell. When the ras gene has been mutated a steady signal is sent to the myc gene. The mutated ras gene causes the cell to grow uncontrollably, and to subsequently cause a tumor (Author Unknown 1997; Parker 1999).
VI. TREATMENTS
The human body has some defense mechanisms against any mutated cell. This mechanism is called apoptosis. Apoptosis allows the body to rid itself of mutated or damaged cells. In this system a damaged or mutated cell commits suicide. Studies show that this process can happen to oncogenes. A tumor forms from an oncogene that some how avoided the process of apoptosis. An oncogene that avoids apoptosis is very dangerous to the body. The subsequent tumor that forms could resist any form of cancer therapy. Other forms of treatments would include radiation and the use of chemotherapeutic drugs. These therapies work to kill the mutated oncogenes by damaging their DNA. By damaging the DNA the cells will kill themselves by apoptosis. Another way the body deals with cells is to limit the amount of times a cell can replicate itself. Another way to prevent normal cells from changing into cancerous cells is to find a treatment that would inhibit the formation of telemerase (Author Unknown 1997; Weinberg 1996).
Scientists feel that once they figure out how oncogenes work they can use that knowledge to inhibit the growth of oncogenes. Once they learn how to turn the replication switch off they may learn how to prevent the spread of cancer. They could prevent the cancer by developing drugs to turn off the replication switch (Fradin 1989).
VII. P53
The oncogene p53 is a tumor suppressor. This oncogene is found on chromosome 17p. The p53 oncogene is found in tumors in the lungs, colon, and breasts. This gene also causes Li-Fraumeni syndrome. Li-Fraumeni syndrome is a syndrome in which tumors are found in the body at multiple sites. This gene is responsible for protecting the cell’s DNA. It repairs the DNA if it is damaged during DNA replication or the replication of cells. Oncogene p53 is responsible for the death of mutated or damaged cells. This prevents the replication of the damaged cells. In sixty percent of the cancer cases the p53 oncogene is mutated. The p53 oncogene is the most commonly found mutated gene in human cancers. Improperly functioning p53 is found in over fifty percent of human tumors (Carbone and Minna 1993; Henderson 2000; Nowell 1991; Weinberg 1996).
VIII. RAS
Studies have shown that in the forty percent of cancer cases in which the p53 oncogene is still intact that the ras oncogene is suppressing the activity of the p53 oncogene. If the research on drugs that prevent the ras oncogene from turning the p53 oncogene off prove effective this could be a way to cause the cancer cells to die. The new drugs could possibly become a new treatment for cancer. Normal and mutated forms of ras can turn the p53 oncogene on (Henderson 2000).
IX. RB
The rb oncogene is also a tumor repressor gene. It is found on the 13q chromosome. Rb is responsible for retinoblastoma and lung cancer. Retinoblastoma is a form of eye cancer. Most human cells divide about fifty to sixty times. Once human cells have divided that many times the cell stops dividing, unless the rb and p53 oncogenes are acting improperly. Once these genes have been mutated the cells divide more than they are suppose to divide (Carbone and Minna 1993; Weinberg 1996).
X. SUMMARY
The mutation of proto-oncogenes causes the formation of oncogenes. Oncogenes can be good for the body by helping to prevent cancer or regulating the amount of protein in the body. Oncogenes can also be harmful to the body by causing the growth of tumors or the onset of cancer. There are many different types of oncogenes that cause many different types of cancer.
XII. TABLE
ONCOGENES
Leukemia abl, c-Myc, N-myc, L-myc, and N-ras
Tumor forming Ha-ras, N-ras, and Ki-ras
Affects the amount of protein
fes and fgr
in the body
Lung cancer L-myc, c-Myc, and Ki-ras
Epidermal growth
erbB
Encoding gene
fms
Transcription factor
L-myc, ets, myc, and jun
Breast cancer
erb-B, erb-B2, c-Myc, N-myc, L-myc, and Bcl-1
TABLE 1. Types of Oncogenes and the cancer or disease they cause. (Author Unknown 2001B; Davis 1999).
XI. REFERENCES
1. Author unknown. 1995. Oncogenes and tumor suppresors [Annual Report of The Howard Hughes Medical Institute]. Retrieved April 2, 2001, from the World Wide Web: http://www.hhmi.org/communic/annrep/research/oncogene.htm
2. Author unknown. 1996. Oncogenes [Scientific America]. Retrived January 24, 2001, from the World Wide Web: http://www.ultranet.com/~jkimball/BiologyPages/O/Oncogenes.html
3. Author Unknown. 1997. MMCG- cellular and viral oncogenes. Retrieved January 25, 2001, from World Wide Web: http://www.biochem.ualberta.ca/Biochem/Dept/Groups/MMCGOncogenes.html
4. Author Unknown. 1999. Human cells converted to cancer cells by expression of telomerase, oncogenes [OncoLink Cancer News Reuters Health Information]. Retrieved March 29, 2001, from World Wide Web: http://cancer.med.upenn.edu/cancer_news/reuters/1999/jul/sc07299b.html
5. Author Unknown. 2001A. Cancer and the immune system the vital connection [Cancer Research Institute]. Retrieved Feburary 6, 2001, from World Wide Web: http://www.cancerresearch.org/immonco.html
6. Author Unknown. 2001B. Oncogenes…and proto-oncogenes. Retrieved February
6, 2001. from World Wide Web http://www.cancergenetics.org/onco.htm
7. Carbone, D. P.; Minna, J. D. 1993. Antioncogenes and human cancer. Annual Review of Medicine 44:451-464.
8. Davis, A. 1999. Discovery of oncogenes. Retrieved February 6, 2001, from
World Wide Web http://www.iona.edu/faculty/csackerson/cancer/disconc.htm
9. Fradin, D. P. 1989. Medicine: yesterday, today, and tomorrow. Childrens Press, Chicago, Illinois.
10. Henderson, C. W. 2000. Study offers insight into cancer development, resistance to therpy; finding focuses on ras oncogene [Cancer Weekly]. Retrieved March 30, 2001, from the World Wide Web: http://…/print2.asp?records=CURRENT&pFormat=PrintCitation&FullText=ON&kwic=on&pPDF=O
11. Nowell, P. C. 1991. How many human cancer genes? [Journal of the National Cancer Institute]. Retreved March 30, 2001, from the World Wide Web: http://sks8.sirs.com/cgi-bin/hst-clean-copy?id=AL0000-s63013en&type=ART&artno+079005
12. Parker, E. 1999. Researchers determine interactions between 2 common oncogenes [The Chronicle online]. Retrieved January 25, 2001, from the World Wide Web: http//www.chronicle.duke.edu/chronicle/1999/03/03/04Researchsdetermine.html
13. Sachs, L. 1986. Growth, differentiation and the reversal of malignancy. Scientific American 254(1) 40-47.
14.
Weinberg, R. A. 1996. How cancer arises [Scientific American].
Retrieved March 5,
2001, from the World Wide Web: http://www.sciam.com/0996issue/0996weinberg.html
Last updated on May 9, 2002 by Jackie Grace.