Protooncogenes: Difference between revisions
Feedback

From WikiLectures

(correction of first half)
(→‎Cellular and Viral Oncogenes: corrected spelling mistake)
 
(8 intermediate revisions by 5 users not shown)
Line 1: Line 1:
{{Was checked|20120215172551| [[User:OSeda|Ondřej Šeda, MD, PhD]]|8311}}
__NOTOC__
__NOTOC__
'''Protooncogenes''' are [[gene]]s that code for proteins responsible for proliferation. If a mutation occurs in protooncogene, there is an increase in protein expression, hyperactivity and loss of regulation. This mutated form is called '''oncogene'''.
'''Protooncogenes''' are [[gene]]s that code for proteins responsible for proliferation. [[Mutation]]s in protooncogenes can lead to an increase in protein expression, hyperactivity (i.e. gain-of-function ) and/or loss of regulation. This mutated form is called '''oncogene'''.


Another mechanism leading to tumor proliferation is a mutation of antiproliferative ''tumor-suppressor genes''. Usually, both copies of tumor-suppressor gene have to be mutated so the effect is manifested (two-hit hypothesis). Protooncogenes, however, differ in that area – [[mutation]] of one copy of the protooncogene to oncogene is often sufficient.
Another mechanism leading to tumor proliferation is a mutation of antiproliferative ''tumor-suppressor genes''. Usually, both copies of tumor-suppressor gene have to be mutated so the effect is manifested (two-hit hypothesis). Protooncogenes, however, differ in that area – [[mutation]] of one copy of the protooncogene to oncogene is often sufficient to induce cancer. There are several possible ways of protooncogene activation:
* '''point-mutation''';
* '''amplification''' (many copies of normal oncogene);
* '''translocation to a transcriptionally active site''' (e.g. Burkitt lymphoma due to translocation of ''MYC'' oncogene into immunoglobulin locus);
* '''chimeric (fusion) gene creation due to chromosomal rearrangement''' (e.g. Philadelphia chromosome).


[[File:Oncogene.jpg|thumb|300 px| Difference between normal cell and cancerous cell.]]
[[File:Oncogene.jpg|thumb|300 px| Difference between normal cell and cancerous cell.]]
Protooncogenes can encode a wide variety of proteins with multiple functions (cell differentiation genes, signaling molecules, surface receptors, regulatory genes, ...). If there is damage to signaling pathways e.g proteins, it may alter the reactivity of cells to the action of growth factors and significantly increase [[cell division]]. This may be caused by ''several mechanisms'':
Protooncogenes can encode a wide variety of proteins with multiple functions (cell differentiation genes, signaling molecules, surface receptors, [[cell cycle]] regulatory genes, secreted growth factors ...). The functional consequences of protooncogene activation include situations when:
* protein begins to be formed in cells in which they normally do not form;
* protein begins to be formed in cells in which they normally do not form;
* protein is made in appropriate cells, but in excessive amounts;
* protein is made in appropriate cells, but in excessive amounts;
* protein is formed in a form that can not be regulated by normal mechanisms.
* protein is formed in a form that can not be regulated by normal mechanisms.


== Examples of (proto)Oncogenes ==
Currently, about '''40 genes are known to be protooncogenes'''. In 16 of them direct correlation with tumor proliferation was shown, such as:
Currently, about '''40 genes are known to be protooncogenes'''. In 16 of them direct correlation with tumor proliferation was shown, such as:
* ''Her-2/neu'': [[breast cancer]];
* ''ERBB2 (HER2)'': [[breast cancer]], by amplification;
* ''K-ras'': tumors of the eosophagus, colon, pancreas;
* ''KRAS'': tumors of the eosophagus, colon, pancreas, by point mutation;
* beta-Catenin: [[Pancreatic cancer]];
* beta-Catenin: [[Pancreatic cancer]];
* Cyclin E: liver tumors;
* Cyclin E: liver tumors;
* mutant ''B-Raf'': [[melanoma]]s.
* ''BRAF'': [[melanoma]]s;
* ''BCR-ABL'': [[chronic myeloid leukemia]].


== Cellular and Viral Oncogenes ==
Oncogenes were originally identified in viruses causing cancers. These are called ''transformation viruses'' (often retrovirus) as they change the growth pattern of cells from normal to tumor-like. The viral oncogenes are designated with an "'''v-'''" prefix, such as '''''v-src'' gene'''. The viral oncogenes originated as copies of cellular protooncogenes, designated with an "'''c-'''" prefix. So the ''v-myc'' is the viral homologue of ''C-MYC'' (i.e. ''MYC'' gene, as is reflected in its official gene name: v-myc myelocytomatosis viral oncogene homolog (avian) ).


== Examples of (proto) oncogenes ==
'''Viral oncogenes – normal function of protooncogene – tumors caused by mutations:'''
Among oncogenes include forms derived growth factor PDGF, receptors of growth hormones or proteins, intracellular signaling pathways. All these cells are characterized by similar behavior – responding as if they constantly receive instructions for signaling division. The cells are so completely beyond regulatory control.
* ''v-abl'' – Tyr-specific protein kinase – pre-B-lymphocytic leukemia;
 
* ''v-erbb'' – epidermal growth factor receptor (''EGFR'') – erythroleukemia;
 
* ''v-fos'', ''v-jun'', ''v-myc'' – gene regulation (DNA-binding protein)osteosarcomas, fibrosarcomas;
Among oncogenes include the viral '''''src'' gene'''. Viruses that cause cancer are called ''transformation viruses'' (often it is a retrovirus). Normally, the src protein kinase regulates genes controlling cell division. Individual structures of oncogene and protooncogene differ in several amino acids.
* ''v-src'' – Tyr-specific protein kinase – sarcomas.
 
 
'''Viral oncogenes – normal function protooncogene – tumors caused by mutations:'''
* ''abl'' oncogene – Tyr-specific protein kinase – pre-B-lymphocytic leukemia;
* ''crest-B'' – epidermal growth factor (EGF) – erythroleukemia;
* ''fos'', ''jun'' – gene regulation – osteosarcomas, fibrosarcomas;
* ''myc'' – regulation of gene expression sarcomas and carcinomas;
* ''src'' – Tyr-specific protein kinase – sarcomas.


<noinclude>
<noinclude>
Line 56: Line 57:
| isbn = 978-1-4160-2973-1
| isbn = 978-1-4160-2973-1
}}
}}
 
* {{Cite
| type = book
| surname1 = STRACHAN, Tom - READ, Andrew
| title = Human Molecular Genetics
| edition = 4
| year = 2010
| isbn = 978-0-8153-4149-9
}}
</noinclude>
</noinclude>



Latest revision as of 23:20, 22 May 2016

This article was checked by pedagogue
This article was checked by pedagogue  

This article ws checked by pedagogue, but later was changed.

Checked version of the article can be found here.

See also comparation of actual and checked version.

Changed checked article.png

Protooncogenes are genes that code for proteins responsible for proliferation. Mutations in protooncogenes can lead to an increase in protein expression, hyperactivity (i.e. gain-of-function ) and/or loss of regulation. This mutated form is called oncogene.

Another mechanism leading to tumor proliferation is a mutation of antiproliferative tumor-suppressor genes. Usually, both copies of tumor-suppressor gene have to be mutated so the effect is manifested (two-hit hypothesis). Protooncogenes, however, differ in that area – mutation of one copy of the protooncogene to oncogene is often sufficient to induce cancer. There are several possible ways of protooncogene activation:

  • point-mutation;
  • amplification (many copies of normal oncogene);
  • translocation to a transcriptionally active site (e.g. Burkitt lymphoma due to translocation of MYC oncogene into immunoglobulin locus);
  • chimeric (fusion) gene creation due to chromosomal rearrangement (e.g. Philadelphia chromosome).
Difference between normal cell and cancerous cell.

Protooncogenes can encode a wide variety of proteins with multiple functions (cell differentiation genes, signaling molecules, surface receptors, cell cycle regulatory genes, secreted growth factors ...). The functional consequences of protooncogene activation include situations when:

  • protein begins to be formed in cells in which they normally do not form;
  • protein is made in appropriate cells, but in excessive amounts;
  • protein is formed in a form that can not be regulated by normal mechanisms.

Examples of (proto)Oncogenes[edit | edit source]

Currently, about 40 genes are known to be protooncogenes. In 16 of them direct correlation with tumor proliferation was shown, such as:

Cellular and Viral Oncogenes[edit | edit source]

Oncogenes were originally identified in viruses causing cancers. These are called transformation viruses (often retrovirus) as they change the growth pattern of cells from normal to tumor-like. The viral oncogenes are designated with an "v-" prefix, such as v-src gene. The viral oncogenes originated as copies of cellular protooncogenes, designated with an "c-" prefix. So the v-myc is the viral homologue of C-MYC (i.e. MYC gene, as is reflected in its official gene name: v-myc myelocytomatosis viral oncogene homolog (avian) ).

Viral oncogenes – normal function of protooncogene – tumors caused by mutations:

  • v-abl – Tyr-specific protein kinase – pre-B-lymphocytic leukemia;
  • v-erbb – epidermal growth factor receptor (EGFR) – erythroleukemia;
  • v-fos, v-jun, v-myc – gene regulation (DNA-binding protein)– osteosarcomas, fibrosarcomas;
  • v-src – Tyr-specific protein kinase – sarcomas.


Links[edit | edit source]

Related articles[edit | edit source]

External links[edit | edit source]

Bibliography[edit | edit source]

  • ALBERTS, B – BRAY, D – JOHNSON, A,. Základy buněčné biologie. 2. vydání edition. 2005. ISBN 80-902906-2-0.
  • KUMAR, VINAY – ABBAS, ABUL K – FAUSTO, NELSON, ET AL,. Robbins basic pathology. 8. edition. 2008. ISBN 978-1-4160-2973-1.
  • STRACHAN, TOM - READ, ANDREW,. Human Molecular Genetics. 4. edition. 2010. ISBN 978-0-8153-4149-9.