Biology:Ectopic expression
Ectopic is a word used with a prefix ecto-, meaning “out of”, and the suffix -topic, meaning "place." Ectopic expression is an abnormal gene expression in a cell type, tissue type, or developmental stage in which the gene is not usually expressed.[1][2] The term ectopic expression is predominantly used in studies using metazoans, especially in Drosophila melanogaster for research purposes.
How is it used
Although ectopic expression can be caused by a natural condition,[1] it is uncommonly seen in nature because it is a product of defects in gene regulation. In fact, ectopic expression is more commonly used for research purposes. Artificially induced gene expression helps to determine the function of a gene of interest. Common techniques such as overexpressing or misexpressing the genes by UAS-Gal4 system in D. melanogaster are used.[2] In model organisms, such techniques are used to perform genetic screens to identify a function of the gene involved in specific cellular or developmental processes.[3]
Ectopic expression using these techniques is a useful tool because phenotypes induced in a tissue or cell type where are not normally expressed are easily distinguishable compared to a tissue or cell type where the gene is normally expressed. By the comparison with its basal expression, the function of a gene of interest can be identified.[3]
Although the understanding of ectopic expressions deals with endogenous genes in an organism, it can be expended to a similar concept like transgenesis, which an exogenous gene is introduced to a cell or tissue type in which the gene is not usually expressed.[4] Practices of ectopic expression in biological science is not only limited to identifying a function of the gene in a known cell or tissue type but also implemented to discover unknown or additional functions of the gene by ectopic expression.
Research examples
Paired box protein
Paired box protein Pax-6 in humans is a transcription factor, which is a main regulatory gene of eye and brain development.[5] Ectopic expression of Drosophila homolog eyeless (ey) has been used to identify roles of Pax-6 in humans. Using tissue specific UAS-Gal4 system, ey can be induced on the legs, wings, halters and antennae of the transgenic flies to demonstrate that functions of ey.[6]
Olfactory receptor genes
Olfactory receptor gene (OR) is normally expressed in human and mouse olfactory tissue with a main function as odorant receptor for the detection of odorants.[7] Individuals with a defect in this gene have disorders of taste and smell. It has been reported that ORs is also expressed on sperms and testis with special emphasis in a manner of ectopic expression. In a study, researchers identified ectopic expression of OR genes in non-olfactory tissues in the mouse model by measuring transcript levels.[8] Here they found relatively low OR gene expression compared to the olfactory tissue, which result indicates that the OR gene in other tissue have no extra function, but they suggest that there is a possibility that small OR subsets can have functional roles in different tissue.[8]
Synovial Sarcoma X chromosome breakpoint-2
Synovial Sarcoma X chromosome breakpoint-2 (SSX2) proteins are known to localize in nucleus and work as a transcriptional repressor. In addition, expression of SSX2 is frequently observed in melanoma,[9] but the role of the gene has not been evaluated. Thus, researchers have used the principle of ectopic expression to express SSX2 to different cell lines including cancer model cells. They found important phenotypes of ectopic SSX2 expression that is involved in tumorigenesis: 1) immediate induction of genomic instability, 2) long-term support of tumor cell growth.[10]
References
- ↑ 1.0 1.1 Cox, Timothy C.; Camci, Esra D.; Vora, Siddharth; Luquetti, Daniela V.; Turner, Eric E. (2014). "The genetics of auricular development and malformation: New findings in model systems driving future directions for microtia research". European Journal of Medical Genetics 57 (8): 394–401. doi:10.1016/j.ejmg.2014.05.003. PMID 24880027.
- ↑ 2.0 2.1 Merriam, John R. (2001). "Genes with ectopic expression phenotypes are common, not rare". Molecular Cell and Developmental Biology 84: 130–132. http://www.ou.edu/journals/dis/DIS84/R39%20Akieda/Akieda.pdf.
- ↑ 3.0 3.1 Rodríguez-Trelles, Francisco; Tarrío, Rosa; Ayala, Francisco J. (2005-06-01). "Is ectopic expression caused by deregulatory mutations or due to gene-regulation leaks with evolutionary potential?" (in en). BioEssays 27 (6): 592–601. doi:10.1002/bies.20241. ISSN 1521-1878. PMID 15892118.
- ↑ Klebig, M. L.; Wilkinson, J. E.; Geisler, J. G.; Woychik, R. P. (1995-05-23). "Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur" (in en). Proceedings of the National Academy of Sciences 92 (11): 4728–4732. doi:10.1073/pnas.92.11.4728. ISSN 0027-8424. PMID 7761391. Bibcode: 1995PNAS...92.4728K.
- ↑ Hanson, Isabel M. (2003-12-01). "PAX6 and Congenital Eye Malformations" (in en). Pediatric Research 54 (6): 791–796. doi:10.1203/01.PDR.0000096455.00657.98. ISSN 0031-3998. PMID 14561779.
- ↑ Kozmik, Zbynek; Daube, Michael; Frei, Erich; Norman, Barbara; Kos, Lidia; Dishaw, Larry J.; Noll, Markus; Piatigorsky, Joram (November 2003). "Role of Pax Genes in Eye Evolution". Developmental Cell 5 (5): 773–785. doi:10.1016/s1534-5807(03)00325-3. PMID 14602077.
- ↑ Malnic, Bettina; Godfrey, Paul A.; Buck, Linda B. (2004-02-24). "The human olfactory receptor gene family" (in en). Proceedings of the National Academy of Sciences of the United States of America 101 (8): 2584–2589. doi:10.1073/pnas.0307882100. ISSN 0027-8424. PMID 14983052. Bibcode: 2004PNAS..101.2584M.
- ↑ 8.0 8.1 Feldmesser, Ester; Olender, Tsviya; Khen, Miriam; Yanai, Itai; Ophir, Ron; Lancet, Doron (2006-01-01). "Widespread ectopic expression of olfactory receptor genes". BMC Genomics 7: 121. doi:10.1186/1471-2164-7-121. ISSN 1471-2164. PMID 16716209.
- ↑ Smith, Heath A.; McNeel, Douglas G. (2010-01-01). "The SSX family of cancer-testis antigens as target proteins for tumor therapy". Clinical & Developmental Immunology 2010: 150591. doi:10.1155/2010/150591. ISSN 1740-2530. PMID 20981248.
- ↑ Greve, Katrine B.V.; Lindgreen, Jonas N.; Terp, Mikkel G.; Pedersen, Christina B.; Schmidt, Steffen; Mollenhauer, Jan; Kristensen, Stine B.; Andersen, Rikke S. et al. (2015-02-01). "Ectopic expression of cancer/testis antigen SSX2 induces DNA damage and promotes genomic instability" (in en). Molecular Oncology 9 (2): 437–449. doi:10.1016/j.molonc.2014.09.001. ISSN 1878-0261. PMID 25363656.
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