Wednesday, 23 May 2012

PAX Genes and Oncogenesis



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PAX genes have been found to regulate cell cycles in tissues where they are commonly expressed. It is widely acknowledged that they play large roles in early and continued formation of the eye, brain, thymus and minimally expressed in a much wider range of tissues. PAX gene expression has thus far shown to provide cells with stem-cell like qualities, providing biochemical pathways to incur tissue repair and regulation of the cell cycle when expressed in adult cells, dependant on the cell context (Li & Eccles 2012).  Fig. 1 shows the results of a non-functional PAX6 gene in eye organogenesis across a range of phyla. Based on this finely tuned ability to facilitate or block cell reproduction in complex tissues, it becomes logical to assume that any deregulation of or disruption to such a specified group of genes could have drastic consequences (Li & Eccles 2012). 

Figure 1: Influence of PAX6 on eye organogenesis (University of Utah 2012)

These results, and the general trend in modern genetics that PAX genes give vital information as to the functioning and formation of cancers, provides a very viable option for possible cancer treatment and probably closer in the future and more practically, a diagnostic marker.
<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269002/pdf/fgene-03-00006.pdf>. This however, requires further diligence in the study and progression of such development, but the benefits of such work are highly tangible with the possibilities of practical and efficient new medical techniques being developed in order to combat cancers in adult tissues.
In recent years significant research has been launched into the sequencing and function of a specific group of genes called PAX or paired box genes. They stand alone as an individual family of genes crucial in embryology and in this sense are very similar to HOX or homeobox genes (Pichaud & Desplan 2002). They function mainly in organogenesis during embryo development, again much like HOX genes. Where they begin to differ is their role following birth and into the construction of adult tissue (Pichaud & Desplan 2002). For further background information on the role of PAX genes visit http://ghr.nlm.nih.gov/geneFamily/pax.  


Figure 2: Basic structural differences of separate PAX genes and contribution to cancer formation (Robinson et al. 2006)



Particularly with diseases such as cancer, which is effectively the proliferation of uncontrolled cell division to harmful ends within a tissue, knowledge of the PAX gene group and its workings in adult tissues could provide inroads into a possible method of preventing cancer mitosis in some tissues (Li & Eccles 2012). Both figures 2 and 3 display the structural and functional differences of separate PAX genes in relation to cancer generation, of course these have become somewhat out-dated since 2006 and as such should be modified to a degree. For example, of the range of 9 PAX genes, PAX6 has been identified as having significant ties to the formation of breast cancer (Xiangyun et al. 2011). During a study conducted at the Zhejiang Provincial Cancer Hospital in early 2011 it was found that by knocking out the PAX6 gene, through the use of a lentivirus, the cell reproduction of a cancerous cell colony was severely compromised and cell viability and plasticity were suppressed (Xiangyun et al. 2011). Further analysis in the results showed a higher rate of tumorous cells suspended in the G0/G1 phase of the cell cycle following the PAX6 knockout, implying that PAX6 expression is necessary for cancer proliferation (Xiangyun et al. 2011). The study itself can be found at :<http://www.jbmb.or.kr/jbmb/jbmb_files/%5B44-9%5D1109261656_(595-600)BMB11-027.pdf>. 

Figure 3: Diagram of PAX gene effects (Robinson et al. 2006)

Of course, such research as this is still simplistic and narrowly focused on a single gene with regards to a single cancer. The wider role of PAX genes in normal tissues and tumorigenesis is still only vaguely defined and holds wide ranges of potential for future development (Li & Eccles 2012). For a wider review of PAX gene literature, visit:<http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3269002/pdf/fgene-03-00006.pdf>. This however, requires further diligence in the study and progression of such development, but the benefits of such work are highly tangible with the possibilities of practical and efficient new medical techniques being developed in order to combat cancers in adult tissues.  
Edward Justo

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