zinc finger protein 703 | |
---|---|
Identifiers | |
Symbol | ZNF703 |
NCBI gene | 80139 |
HGNC | 25883 |
RefSeq | NM_025069 |
Other data | |
Locus | Chr. 8 p12 |
ZNF703 is a gene which has been linked with the development of breast cancers. [5] [6] [7] ZNF703 is contained within the NET/N1z family responsible for regulation of transcription essential for developmental growth especially in the hindbrain. [8] Normal functions performed by ZNF703 include adhesion, movement and proliferation of cells. [8] ZNF703 directly accumulates histone deacetylases at gene promoter regions but does not bind to functional DNA. [9]
Following research by scientists at Cancer Research UK, it was the first oncogene discovery in the past six years. [6]
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. [10]
Patients diagnosed with luminal B cancer caused by ZNF703 typically have lower recovery and survival rates than other cancer types. [11]
Drug resistance of ZNF703 has been displayed when patients are treated using anti-cancer drug Tamoxifen. [12]
Researchers discovered the carcinogenic nature of ZNF703 in 2011 while conducting research on the classification and resistance of various oncogenes. [8] Researchers attempted to discern factors associated with various cancer types through observation of the oncogenic mechanism on a molecular scale. [8] The luminal B cancer pathway exhibited an amplification of 5 different genomic areas including the chromosome region 8p12. [8] Amplification of region 8p12 occurred through transcriptional regulation of ZNF703. [8]
ZNF703 is located on human chromosome 8 at the short arm region commonly named chromosome region 8p12. [5] 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. [13] A fluctuation between increase and decrease is present along the 8p12-8p21 boundary region of the chromosome. [13] 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. [13]
The ZNF703 gene generally plays an active role in luminal B tumor cells contained in mammary ducts. [5] Typically, ZNF703 expression is greater when the tumors are estrogen receptor positive as opposed to estrogen receptor negative. [5] ZNF703 is co-expressed in a nuclear complex containing genes DCAF7, NCRO2 and PHB2. [5] ZNF703 generates a nuclear protein responsible for oestrogen receptor associated protein repression. [5] Gene expression of stem cells are triggered when the ZNF703 gene becomes overexpressed in the complex. [5] As a result, both regular cells and cancer stem cell abundance increases rapidly. [5] ZNF703 overexpression also causes primary and secondary tumorsphere development alongside amplified production of CD49F- positive cells associated with colon cancer. [5]
ZNF703 also experiences target regulation of cancer cells through the transcription of RNA SPRY4-It1. [14] RNA SPRY4-IT1 is a non-coding gene responsible for preventing apoptosis and generating large tumors. [14]
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. [15]
The lifespan of individuals with colorectal cancer and luminal cancer have different prognosis depending on the amount of expression of the ZNF703 gene. [11] Low amounts of transcription of ZNF703 usually leads to a healthier prognosis than individuals experiencing higher levels of transcription of the oncogene. [11] ZNF703 is a target for therapeutic medicines since survival rates increase as transcription rates decrease. [11]
The drug Tamoxifen is a commonly administered drug used to treat luminal cancers in patients. [12] Half of patients treated with Tamoxifen are resistant to the drug. [12] Overexpression of ZNF703 has been linked to Tamoxifen resistance. [12] As transcription of the ZNF703 gene reaches substantial levels, instead of blocking cell proliferation, Tamoxifen is found to increase cancer cell division. [12] Tamoxifen can only be given at low dosages and patients are monitored daily in order to avoid tumor growth. [12]