Disease relevance of PAX2

• Mutation of the PAX2 gene in a family with optic nerve colobomas, renal anomalies and vesicoureteral reflux [1].
• We have conducted a mutational analysis of PAX2 in a family with optic nerve colobomas, renal hypoplasia, mild proteinuria and vesicoureteral reflux [1].
• This report describes the cloning and characterization of the human PAX2 gene promoter and localization of the transcription start sites in fetal kidney and Wilms' tumor [2].
• We cloned PAX2 from Kaposi's sarcoma cells and obtained antisense and sense DNA [3].
• Optic nerve dysplasia and renal insufficiency in a family with a novel PAX2 mutation, Arg115X: further ophthalmologic delineation of the renal-coloboma syndrome [4].
• We show that both loss of VHL protein (pVHL) function and hypoxia leads to strong PAX2 reexpression [5].

Psychiatry related information on PAX2

• Expression of PAX2 gene during human development [6].

High impact information on PAX2

• The phenotype resulting from the PAX2 mutation in this family was very similar to abnormalities that have been reported in Krd mutant mice [1].
• The PAX2 gene is expressed in primitive cells of the kidney, ureter, eye, ear and central nervous system [1].
• The developmental gene, PAX2, located within this region, is an attractive candidate gene [7].
• The anterior border of the tectum might be determined as a result of repressive interaction of Pax6 with En1 and Pax2 [8].
• It is proposed that the brain vesicle that expresses Otx2, Pax2 and En1 might differentiate into the tectum [8].

Chemical compound and disease context of PAX2

• Expression of the PAX2 oncogene in human breast cancer and its role in progesterone-dependent mammary growth [9].
• Our experiments show that PAX2 is activated by oestrogen and tamoxifen in endometrial carcinomas but not in normal endometrium, and that this activation is associated with cancer-linked hypomethylation of the PAX2 promoter [10].

Biological context of PAX2

• In this study, we found that Kaposi's sarcoma cells but not human microvascular endothelial cells expressed PAX2, a gene coding for a transcription factor involved both in organogenesis and tumorigenesis [3].
• The nucleotide changes for patients 1 and 2 directly introduced stop codons, presumably resulting in a message for a truncated PAX2 protein that lacked a partial transactivation domain [11].
• The paired-box transcription factor, PAX2, positively modulates expression of the Wilms' tumor suppressor gene (WT1) [12].
• Deletion mutagenesis of the wt1 promoter identified an element responsible for mediating PAX2 responsiveness, located between nucleotides -33 and -71 relative to the first wt1 transcription start site [12].
• Apoptosis was rapidly induced in ovarian and bladder cancer cell lines following RNA interference to silence PAX2 expression, despite concomitant TP53 and/or HRAS mutations [13].

Anatomical context of PAX2

• In contrast, PAX2 expression was present mainly in the very early stages of differentiation, in the induced, condensing mesenchyme [14].
• We demonstrate that WT1 mislocalization is associated with abnormal podocyte expression of PAX2 protein and RNA [15].
• Endothelial cells transfected with sense PAX2 acquired spindle shape morphology, showed enhanced motility and Matrigel invasion, and displayed an enhanced expression of alphavbeta3 integrin [3].
• PAX2 encodes a transcription factor of the paired box class of DNA binding proteins, important for the development of the urogenital tract, optic nerve and adjacent retina, inner ear, and CNS [16].
• By somatic cell hybrid mapping, the PAX2 gene was localized to chromosome 10q22.1-q24.3, although this region has not previously been implicated in Wilms' tumor [17].

Associations of PAX2 with chemical compounds

• To determine whether restoration of antiapoptotic factors alone is sufficient to rescue the nephron deficit in these mice, a BCL2 transgene that is under the control of the PAX2 promoter was targeted to the ureteric bud [18].
• In the mouse, mammary parenchyma with a targeted deletion of PAX2 developed normal ductal systems when grafted into wild-type host mammary fat pads, but failed to undergo higher order side-branching and lobular development in response to progesterone [9].
• In addition to a DNA binding domain, the Pax2 protein contains a carboxyl-terminal transactivation domain rich in serine, threonine, and tyrosine [19].
• In this study we hypothesized that PAX2 activates expression of WNT4, a secreted glycoprotein known to be critical for successful nephrogenesis [20].
• PAX2 inactivation enhances cisplatin-induced apoptosis in renal carcinoma cells [21].

Co-localisations of PAX2

• The PAX2 signal co-localized more with cytokeratin staining than with vimentin [22].

Regulatory relationships of PAX2

• Phosphorylation of Pax2 by the c-Jun N-terminal kinase and enhanced Pax2-dependent transcription activation [19].
• In contrast, Pax3-negative cells in the grafted ectoderm are induced to express the epibranchial placode marker Pax2 and form neurons in the nodose ganglion that express the epibranchial neuron marker Phox2a on the same schedule as host nodose neurons [23].
• PAX2 Activates WNT4 Expression during Mammalian Kidney Development [20].
• These cells lacked the expression of hematopoietic markers and expressed PAX-2, an embryonic renal marker, suggesting their renal origin [24].

Other interactions of PAX2

• Furthermore, it was indicated that PAX2, GFRA1, and EMX2 on distal 10q, in which the deletions could affect urinary and/or genital development, were present in two copies in cases 1 through 8 [25].
• We have also assigned two previously known genes, PAX2 and CYP17, more precisely into this region, but the sequence analysis of coding regions of these two genes has not revealed mutations in an IOSCA patient [26].
• RNA samples were electrophoretically separated in 1.2% agarose gels, transferred to nylon membranes, and hybridized to random primer-labeled PAX2, PAX8, and WT1 probes [27].
• Comparative in situ hybridization analysis of PAX2, PAX8, and WT1 gene transcription in human fetal kidney and Wilms' tumors [28].
• The entire coding regions of PAX2 and PAX6 were screened for mutations [29].

Analytical, diagnostic and therapeutic context of PAX2

• For investigation of whether PAX2 mutations occur in patients with isolated renal hypoplasia, patient DNA was analyzed for PAX2 mutations, by using PCR and direct sequencing [11].
• Sequencing and restriction mapping of these clones showed that human PAX2 was composed of 12 exons spanning approximately 70 kb [30].
• We have examined the pattern of expression of the human PAX2 gene in Wilms' tumors and human fetal kidney by Northern blot and in situ hybridization [17].
• Molecular genetic analysis of the PAX2 gene in combination with renal ultrasonography can help in making an earlier diagnosis of the disease [31].
• PAX2 is a specific and sensitive immunohistochemical marker in identification and differential diagnosis of nephrogenic adenoma [32].

References