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'''ZNF703'''<ref>http://www.ebi.ac.uk/gxa/gene?gid=Q9H7S9</ref> is a [[gene]] which has been linked with the development of [[breast cancer]]s.<ref name="pmid21328542">{{cite journal |vauthors=Sircoulomb F, Nicolas N, Ferrari A, etal |title=ZNF703 gene amplification at 8p12 specifies luminal B breast cancer |journal=EMBO Molecular Medicine |volume= 3|issue= 3|pages= 153–166|date=February 2011 |pmid=21328542 |doi=10.1002/emmm.201100121 |url= |pmc=3395112}}</ref><ref name=BBC>{{cite news |url= | '''ZNF703'''<ref>http://www.ebi.ac.uk/gxa/gene?gid=Q9H7S9</ref> is a [[gene]] which has been linked with the development of [[breast cancer]]s.<ref name="pmid21328542">{{cite journal |vauthors=Sircoulomb F, Nicolas N, Ferrari A, etal |title=ZNF703 gene amplification at 8p12 specifies luminal B breast cancer |journal=EMBO Molecular Medicine |volume= 3|issue= 3|pages= 153–166|date=February 2011 |pmid=21328542 |doi=10.1002/emmm.201100121 |url= |pmc=3395112}}</ref><ref name=BBC>{{cite news |url=https://www.bbc.co.uk/news/health-12503798 |title=BBC News - Key breast cancer 'driver' gene found |format= |work= |accessdate=2011-02-18 |date=2011-02-18}}</ref><ref name="pmid19330026">{{cite journal |vauthors=Kwek SS, Roy R, Zhou H, etal |title=Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis |journal=Oncogene |volume=28 |issue=17 |pages=1892–903 |date=April 2009 |pmid=19330026 |pmc=2722962 |doi=10.1038/onc.2009.34}}</ref> ZNF703 is contained within the NET/N1z family responsible for regulation of transcription essential for developmental growth especially in the hindbrain.<ref name=":0">{{Cite journal|last=YANG|first=GONGLI|last2=MA|first2=FENG|last3=ZHONG|first3=MUXIAO|last4=FANG|first4=LIN|last5=PENG|first5=YAO|last6=XIN|first6=XIAOMING|last7=ZHONG|first7=JIETAO|last8=YUAN|first8=FANGFANG|last9=GU|first9=HONGXIANG|title=ZNF703 acts as an oncogene that promotes progression in gastric cancer|url=https://www.spandidos-publications.com/|journal=Oncology Reports|volume=31|issue=4|pages=1877–1882|doi=10.3892/or.2014.2997|pmid=24481460|year=2014}}</ref> Normal functions performed by ZNF703 include adhesion, movement and proliferation of cells.<ref name=":0" /> ZNF703 directly accumulates histone deacetylases at gene promoter regions but does not bind to functional DNA.<ref>{{Cite journal|last=Nakamura|first=Mako|last2=Choe|first2=Seong-Kyu|last3=Runko|first3=Alexander P.|last4=Gardner|first4=Paul D.|last5=Sagerström|first5=Charles G.|date=2008-11-12|title=Nlz1/Znf703 acts as a repressor of transcription|journal=BMC Developmental Biology|volume=8|pages=108|doi=10.1186/1471-213x-8-108|pmid=19014486|pmc=2588584|issn=1471-213X}}</ref> | ||
Following research by scientists at [[Cancer Research UK]], it was the first [[oncogene]] discovery in the past six years.<ref name=BBC/> | Following research by scientists at [[Cancer Research UK]], it was the first [[oncogene]] discovery in the past six years.<ref name=BBC/> | ||
ZNF703 is a part of 8p12 telomeric amplicon that is associated with Luminal B breast cancer. Recently, ZNF703 is identified as the driver of 8p12 locus | ZNF703 is a part of 8p12 telomeric amplicon that is associated with Luminal B breast cancer. Recently, ZNF703 is identified as the driver of 8p12 locus amplification.<ref>{{Cite journal|url = |title = ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium|last = Holland|first = Daniel|date = Feb 2011|journal = EMBO Molecular Medicine|doi = 10.1002/emmm.201100122|pmc = 3395113|pmid = 21337521|volume=3|issue = 3|pages=167–80}}</ref> | ||
Patients diagnosed with luminal B cancer caused by ZNF703 typically have lower recovery and survival rates than other cancer types.<ref name=":1">{{Cite journal|last=MA|first=FENG|last2=BI|first2=LIHONG|last3=YANG|first3=GONGLI|last4=ZHANG|first4=MENGNAN|last5=LIU|first5=CUIPING|last6=ZHAO|first6=YINGYING|last7=WANG|first7=YADONG|last8=WANG|first8=JIDE|last9=BAI|first9=YANG|title=ZNF703 promotes tumor cell proliferation and invasion and predicts poor prognosis in patients with colorectal cancer|url=https://www.spandidos-publications.com/|journal=Oncology Reports|volume=32|issue=3|pages=1071–1077|doi=10.3892/or.2014.3313}}</ref> | Patients diagnosed with luminal B cancer caused by ZNF703 typically have lower recovery and survival rates than other cancer types.<ref name=":1">{{Cite journal|last=MA|first=FENG|last2=BI|first2=LIHONG|last3=YANG|first3=GONGLI|last4=ZHANG|first4=MENGNAN|last5=LIU|first5=CUIPING|last6=ZHAO|first6=YINGYING|last7=WANG|first7=YADONG|last8=WANG|first8=JIDE|last9=BAI|first9=YANG|title=ZNF703 promotes tumor cell proliferation and invasion and predicts poor prognosis in patients with colorectal cancer|url=https://www.spandidos-publications.com/|journal=Oncology Reports|volume=32|issue=3|pages=1071–1077|doi=10.3892/or.2014.3313|pmid=25017610|year=2014}}</ref> | ||
[[Drug resistance]] of ZNF703 has been displayed when patients are treated using anti-cancer drug Tamoxifen.<ref name=":2">{{Cite journal|last=Zhang|first=Xi|last2=Mu|first2=Xin|last3=Huang|first3=Ou|last4=Xie|first4=Zuoquan|last5=Jiang|first5=Min|last6=Geng|first6=Meiyu|last7=Shen|first7=Kunwei|date=2013-08-26|title=Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling | [[Drug resistance]] of ZNF703 has been displayed when patients are treated using anti-cancer drug Tamoxifen.<ref name=":2">{{Cite journal|last=Zhang|first=Xi|last2=Mu|first2=Xin|last3=Huang|first3=Ou|last4=Xie|first4=Zuoquan|last5=Jiang|first5=Min|last6=Geng|first6=Meiyu|last7=Shen|first7=Kunwei|date=2013-08-26|title=Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling|journal=PLOS ONE|volume=8|issue=8|pages=e72053|doi=10.1371/journal.pone.0072053|pmid=23991038|pmc=3753350|issn=1932-6203}}</ref> | ||
== Discovery == | == Discovery == | ||
| Line 33: | Line 33: | ||
== Location == | == Location == | ||
[[File:Human chromosome 08 - 550 bphs.png|thumb|Oncogene ZNF703 is located at the p-arm of human chromosome 8 at position 8p12.]] | [[File:Human chromosome 08 - 550 bphs.png|thumb|Oncogene ZNF703 is located at the p-arm of human chromosome 8 at position 8p12.]] | ||
ZNF703 is located on human chromosome 8 at the short arm region commonly named chromosome region 8p12.<ref name="pmid21328542" /> Tumors generated by ZNF703 have shown loss in size beginning at the [[telomere]] and ending at 8p12 while the 8p12-11 region has increased size.<ref name=":3">{{Cite journal|last=Gelsi-Boyer|first=Véronique|last2=Orsetti|first2=Béatrice|last3=Cervera|first3=Nathalie|last4=Finetti|first4=Pascal|last5=Sircoulomb|first5=Fabrice|last6=Rougé|first6=Carole|last7=Lasorsa|first7=Laurence|last8=Letessier|first8=Anne|last9=Ginestier|first9=Christophe|date=2005-12-01|title=Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer | ZNF703 is located on human chromosome 8 at the short arm region commonly named chromosome region 8p12.<ref name="pmid21328542" /> Tumors generated by ZNF703 have shown loss in size beginning at the [[telomere]] and ending at 8p12 while the 8p12-11 region has increased size.<ref name=":3">{{Cite journal|last=Gelsi-Boyer|first=Véronique|last2=Orsetti|first2=Béatrice|last3=Cervera|first3=Nathalie|last4=Finetti|first4=Pascal|last5=Sircoulomb|first5=Fabrice|last6=Rougé|first6=Carole|last7=Lasorsa|first7=Laurence|last8=Letessier|first8=Anne|last9=Ginestier|first9=Christophe|date=2005-12-01|title=Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer|journal=Molecular Cancer Research|volume=3|issue=12|pages=655–667|doi=10.1158/1541-7786.mcr-05-0128|pmid=16380503}}</ref> A fluctuation between increase and decrease is present along the 8p12-8p21 boundary region of the chromosome.<ref name=":3" /> A pattern has been found that involves three similar regions of disrupted growth and four regions of enhanced growth starting from the telomere and ending at the [[centromere]].<ref name=":3" /> | ||
== Role in cancer == | == Role in cancer == | ||
The ZNF703 gene generally plays an active role in luminal B tumor cells contained in mammary ducts.<ref name="pmid21328542" /> Typically, ZNF703 expression is greater when the tumors are [[estrogen receptor]] positive as opposed to estrogen receptor negative.<ref name="pmid21328542" /> ZNF703 is co-expressed in a nuclear complex containing genes DCAF7, NCRO2 and PHB2.<ref name="pmid21328542" /> ZNF703 generates a nuclear protein responsible for oestrogen receptor associated protein repression.<ref name="pmid21328542" /> [[Gene expression]] of [[stem cells]] are triggered when the ZNF703 gene becomes overexpressed in the complex.<ref name="pmid21328542" /> As a result, both regular cells and cancer stem cell abundance increases rapidly.<ref name="pmid21328542" /> ZNF703 overexpression also causes primary and secondary tumorsphere development alongside amplified production of CD49F- positive cells associated with colon cancer.<ref name="pmid21328542" /> | The ZNF703 gene generally plays an active role in luminal B tumor cells contained in mammary ducts.<ref name="pmid21328542" /> Typically, ZNF703 expression is greater when the tumors are [[estrogen receptor]] positive as opposed to estrogen receptor negative.<ref name="pmid21328542" /> ZNF703 is co-expressed in a nuclear complex containing genes DCAF7, NCRO2 and PHB2.<ref name="pmid21328542" /> ZNF703 generates a nuclear protein responsible for oestrogen receptor associated protein repression.<ref name="pmid21328542" /> [[Gene expression]] of [[stem cells]] are triggered when the ZNF703 gene becomes overexpressed in the complex.<ref name="pmid21328542" /> As a result, both regular cells and cancer stem cell abundance increases rapidly.<ref name="pmid21328542" /> ZNF703 overexpression also causes primary and secondary tumorsphere development alongside amplified production of CD49F- positive cells associated with colon cancer.<ref name="pmid21328542" /> | ||
ZNF703 also experiences target regulation of cancer cells through the transcription of RNA SPRY4-It1.<ref name=":4">{{Cite journal|last=Shi|first=Yongguo|last2=Li|first2=Juan|last3=Liu|first3=Yangchen|last4=Ding|first4=Jie|last5=Fan|first5=Yingrui|last6=Tian|first6=Yun|last7=Wang|first7=Li|last8=Lian|first8=Yifan|last9=Wang|first9=Keming|date=2015-02-22|title=The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression | ZNF703 also experiences target regulation of cancer cells through the transcription of RNA SPRY4-It1.<ref name=":4">{{Cite journal|last=Shi|first=Yongguo|last2=Li|first2=Juan|last3=Liu|first3=Yangchen|last4=Ding|first4=Jie|last5=Fan|first5=Yingrui|last6=Tian|first6=Yun|last7=Wang|first7=Li|last8=Lian|first8=Yifan|last9=Wang|first9=Keming|date=2015-02-22|title=The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression|journal=Molecular Cancer|volume=14|pages=51|doi=10.1186/s12943-015-0318-0|pmid=25742952|pmc=4350857|issn=1476-4598}}</ref> RNA SPRY4-IT1 is a non-coding gene responsible for preventing [[apoptosis]] and generating large tumors.<ref name=":4" /> | ||
Researchers recently established a link between the trigger gene ZNF703 and Akt/mTOR pathway activation involved in the cellular cycle resulting in lung tumor formation.<ref>{{Cite journal|last=Baykara|first=Onur|last2=Dalay|first2=Nejat|last3=Kaynak|first3=Kamil|last4=Buyru|first4=Nur|date=2016-10-01|title=ZNF703 Overexpression may act as an oncogene in non-small cell lung cancer | Researchers recently established a link between the trigger gene ZNF703 and Akt/mTOR pathway activation involved in the cellular cycle resulting in lung tumor formation.<ref>{{Cite journal|last=Baykara|first=Onur|last2=Dalay|first2=Nejat|last3=Kaynak|first3=Kamil|last4=Buyru|first4=Nur|date=2016-10-01|title=ZNF703 Overexpression may act as an oncogene in non-small cell lung cancer|journal=Cancer Medicine|language=en|volume=5|issue=10|pages=2873–2878|doi=10.1002/cam4.847|pmid=27650486|pmc=5083741|issn=2045-7634}}</ref> | ||
== Prognosis == | == Prognosis == | ||
| Line 46: | Line 46: | ||
== Resistance to drugs == | == Resistance to drugs == | ||
The drug [[Tamoxifen]] is a commonly administered drug used to treat luminal cancers in patients.<ref name=":2" /> | The drug [[Tamoxifen]] is a commonly administered drug used to treat luminal cancers in patients.<ref name=":2" /> Half of patients treated with Tamoxifen are resistant to the drug.<ref name=":2" /> Overexpression of ZNF703 has been linked to Tamoxifen resistance.<ref name=":2" /> As transcription of the ZNF703 gene reaches substantial levels, instead of blocking cell proliferation, Tamoxifen is found to increase cancer cell division.<ref name=":2" /> Tamoxifen can only be given at low dosages and patients are monitored daily in order to avoid tumor growth.<ref name=":2" /> | ||
==References== | ==References== | ||
| Line 52: | Line 52: | ||
[[Category:Estrogen regulation]] | [[Category:Estrogen regulation]] | ||
Revision as of 21:53, 20 November 2018
| zinc finger protein 703 | |
|---|---|
| Identifiers | |
| Symbol | ZNF703 |
| Entrez | 80139 |
| HUGO | 25883 |
| RefSeq | NM_025069 |
| Other data | |
| Locus | Chr. 8 p12 |
ZNF703[1] is a gene which has been linked with the development of breast cancers.[2][3][4] ZNF703 is contained within the NET/N1z family responsible for regulation of transcription essential for developmental growth especially in the hindbrain.[5] Normal functions performed by ZNF703 include adhesion, movement and proliferation of cells.[5] ZNF703 directly accumulates histone deacetylases at gene promoter regions but does not bind to functional DNA.[6]
Following research by scientists at Cancer Research UK, it was the first oncogene discovery in the past six years.[3]
ZNF703 is a part of 8p12 telomeric amplicon that is associated with Luminal B breast cancer. Recently, ZNF703 is identified as the driver of 8p12 locus amplification.[7]
Patients diagnosed with luminal B cancer caused by ZNF703 typically have lower recovery and survival rates than other cancer types.[8]
Drug resistance of ZNF703 has been displayed when patients are treated using anti-cancer drug Tamoxifen.[9]
Discovery
Researchers discovered the carcinogenic nature of ZNF703 in 2011 while conducting research on the classification and resistance of various oncogenes.[5] Researchers attempted to discern factors associated with various cancer types through observation of the oncogenic mechanism on a molecular scale.[5] The luminal B cancer pathway exhibited an amplification of 5 different genomic areas including the chromosome region 8p12.[5] Amplification of region 8p12 occurred through transcriptional regulation of ZNF703.[5]
Location
ZNF703 is located on human chromosome 8 at the short arm region commonly named chromosome region 8p12.[2] Tumors generated by ZNF703 have shown loss in size beginning at the telomere and ending at 8p12 while the 8p12-11 region has increased size.[10] A fluctuation between increase and decrease is present along the 8p12-8p21 boundary region of the chromosome.[10] A pattern has been found that involves three similar regions of disrupted growth and four regions of enhanced growth starting from the telomere and ending at the centromere.[10]
Role in cancer
The ZNF703 gene generally plays an active role in luminal B tumor cells contained in mammary ducts.[2] Typically, ZNF703 expression is greater when the tumors are estrogen receptor positive as opposed to estrogen receptor negative.[2] ZNF703 is co-expressed in a nuclear complex containing genes DCAF7, NCRO2 and PHB2.[2] ZNF703 generates a nuclear protein responsible for oestrogen receptor associated protein repression.[2] Gene expression of stem cells are triggered when the ZNF703 gene becomes overexpressed in the complex.[2] As a result, both regular cells and cancer stem cell abundance increases rapidly.[2] ZNF703 overexpression also causes primary and secondary tumorsphere development alongside amplified production of CD49F- positive cells associated with colon cancer.[2]
ZNF703 also experiences target regulation of cancer cells through the transcription of RNA SPRY4-It1.[11] RNA SPRY4-IT1 is a non-coding gene responsible for preventing apoptosis and generating large tumors.[11]
Researchers recently established a link between the trigger gene ZNF703 and Akt/mTOR pathway activation involved in the cellular cycle resulting in lung tumor formation.[12]
Prognosis
The lifespan of individuals with colorectal cancer and luminal cancer have different prognosis depending on the amount of expression of the ZNF703 gene.[8] Low amounts of transcription of ZNF703 usually leads to a healthier prognosis than individuals experiencing higher levels of transcription of the oncogene.[8] ZNF703 is a target for therapeutic medicines since survival rates increase as transcription rates decrease.[8]
Resistance to drugs
The drug Tamoxifen is a commonly administered drug used to treat luminal cancers in patients.[9] Half of patients treated with Tamoxifen are resistant to the drug.[9] Overexpression of ZNF703 has been linked to Tamoxifen resistance.[9] As transcription of the ZNF703 gene reaches substantial levels, instead of blocking cell proliferation, Tamoxifen is found to increase cancer cell division.[9] Tamoxifen can only be given at low dosages and patients are monitored daily in order to avoid tumor growth.[9]
References
- ↑ http://www.ebi.ac.uk/gxa/gene?gid=Q9H7S9
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Sircoulomb F, Nicolas N, Ferrari A, et al. (February 2011). "ZNF703 gene amplification at 8p12 specifies luminal B breast cancer". EMBO Molecular Medicine. 3 (3): 153–166. doi:10.1002/emmm.201100121. PMC 3395112. PMID 21328542.
- ↑ 3.0 3.1 "BBC News - Key breast cancer 'driver' gene found". 2011-02-18. Retrieved 2011-02-18.
- ↑ Kwek SS, Roy R, Zhou H, et al. (April 2009). "Co-amplified genes at 8p12 and 11q13 in breast tumors cooperate with two major pathways in oncogenesis". Oncogene. 28 (17): 1892–903. doi:10.1038/onc.2009.34. PMC 2722962. PMID 19330026.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 YANG, GONGLI; MA, FENG; ZHONG, MUXIAO; FANG, LIN; PENG, YAO; XIN, XIAOMING; ZHONG, JIETAO; YUAN, FANGFANG; GU, HONGXIANG (2014). "ZNF703 acts as an oncogene that promotes progression in gastric cancer". Oncology Reports. 31 (4): 1877–1882. doi:10.3892/or.2014.2997. PMID 24481460.
- ↑ Nakamura, Mako; Choe, Seong-Kyu; Runko, Alexander P.; Gardner, Paul D.; Sagerström, Charles G. (2008-11-12). "Nlz1/Znf703 acts as a repressor of transcription". BMC Developmental Biology. 8: 108. doi:10.1186/1471-213x-8-108. ISSN 1471-213X. PMC 2588584. PMID 19014486.
- ↑ Holland, Daniel (Feb 2011). "ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium". EMBO Molecular Medicine. 3 (3): 167–80. doi:10.1002/emmm.201100122. PMC 3395113. PMID 21337521.
- ↑ 8.0 8.1 8.2 8.3 MA, FENG; BI, LIHONG; YANG, GONGLI; ZHANG, MENGNAN; LIU, CUIPING; ZHAO, YINGYING; WANG, YADONG; WANG, JIDE; BAI, YANG (2014). "ZNF703 promotes tumor cell proliferation and invasion and predicts poor prognosis in patients with colorectal cancer". Oncology Reports. 32 (3): 1071–1077. doi:10.3892/or.2014.3313. PMID 25017610.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 Zhang, Xi; Mu, Xin; Huang, Ou; Xie, Zuoquan; Jiang, Min; Geng, Meiyu; Shen, Kunwei (2013-08-26). "Luminal Breast Cancer Cell Lines Overexpressing ZNF703 Are Resistant to Tamoxifen through Activation of Akt/mTOR Signaling". PLOS ONE. 8 (8): e72053. doi:10.1371/journal.pone.0072053. ISSN 1932-6203. PMC 3753350. PMID 23991038.
- ↑ 10.0 10.1 10.2 Gelsi-Boyer, Véronique; Orsetti, Béatrice; Cervera, Nathalie; Finetti, Pascal; Sircoulomb, Fabrice; Rougé, Carole; Lasorsa, Laurence; Letessier, Anne; Ginestier, Christophe (2005-12-01). "Comprehensive Profiling of 8p11-12 Amplification in Breast Cancer". Molecular Cancer Research. 3 (12): 655–667. doi:10.1158/1541-7786.mcr-05-0128. PMID 16380503.
- ↑ 11.0 11.1 Shi, Yongguo; Li, Juan; Liu, Yangchen; Ding, Jie; Fan, Yingrui; Tian, Yun; Wang, Li; Lian, Yifan; Wang, Keming (2015-02-22). "The long noncoding RNA SPRY4-IT1 increases the proliferation of human breast cancer cells by upregulating ZNF703 expression". Molecular Cancer. 14: 51. doi:10.1186/s12943-015-0318-0. ISSN 1476-4598. PMC 4350857. PMID 25742952.
- ↑ Baykara, Onur; Dalay, Nejat; Kaynak, Kamil; Buyru, Nur (2016-10-01). "ZNF703 Overexpression may act as an oncogene in non-small cell lung cancer". Cancer Medicine. 5 (10): 2873–2878. doi:10.1002/cam4.847. ISSN 2045-7634. PMC 5083741. PMID 27650486.