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PAX8 positively regulates the expression of TP53 in high grade serous ovarian carcinoma (HGSC) and the pro-proliferative role of PAX8 is mediated by the gain of function activity of mutant p53. Surprisingly, mutant p53 transcriptionally activates the expression of p21, which localizes to the cytoplasm of HGSC cells where it plays a non-canonical, pro-proliferative role.
PAX8-PPARG fusions may not play major roles in the tumorigenesis of paediatric follicular thyroid carcinoma.
Identify several novel PAX8 mutations in congenital hypothyroidism patients that impair the binding or activating abilities of PAX8 at the promoters of the target genes thyroglobulin and thyroperoxidase.
Data suggest that candidate genes and pathways regulated by PAX8 that could be additional targets for the therapy of ovarian carcinoma.
PAX8 has a cell specific role in governing proliferation and migration in nontransformed ovarian surface epithelium cells compared to the oviductal cells, but its reduction in serous cancer cell lines provides a common mechanism for reducing cell survival.
findings proved that iodinated TG in thyroid follicular lumen regulated TTF-1 and PAX8 expression through thyroid stimulating hormone/thyroid stimulating hormone receptor (TSH/TSHR) mediated cAMP-PKA and PLC-PKC signaling pathways.
Case Report: primary seminal vesicle carcinoma strong and diffuse nuclear labeling for PAX8.
PAX8 is expressed in both benign and malignant mesothelium, and that BAP1 loss is highly specific for malignant peritoneal neoplasms, in the differential with both benign mesothelial proliferations and ovarian serous tumors.
Although the exact biological function remains to be explored, our findings suggest a possible association of PAX8eQTLs in lncRNA AC016683.6 with the hepatocellular carcinoma prognosis in the Chinese population.
findings point to significant PTC-associated dysregulation of several PAX8 target genes, supporting the notion that PAX8-regulated molecular cascades play important roles during thyroid tumorigenesis
we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9)
Putative PAX8 target genes are enriched for common serous epithelial ovarian cancer risk variants.
We conclude that PAX8 immunostain is negative in most cervical cell carcinomas and is less frequently expressed in endocervical adenocarcinomas as compared with the previously reported high sensitivity for ovarian and endometrial adenocarcinomas
Study postulated that both TTF-1 and PAX-8 when co-expressed and have anti-proliferative and anti-tumorigenic properties up to a threshold expression level and beyond that, are able to induce pro-tumorigenic effects in thyroid carcinomas.
Direct sequencing of the PAX8 gene revealed a novel single nucleotide substitution (c.162 A>T) in exon 2 that resulted in the substitution of the normal serine 54 with a cysteine (S54C), which segregated with elevated serum TSH levels.
This is the first report of PAX8 aberrant transcript production in cervical cancer. Reported PAX8 isoforms possess differential transactivation properties; therefore, besides being a helpful marker for detection of cancer, PAX8 isoforms can plausibly exert differential regulation properties during carcinogenesis
PAX2, PAX8, CDX2 immunostains was preformed to the TMA slides.
Pax8 gene Rearrangement is associated with Breast Cancer.
PAX8 was negative in all cases of pulmonary neuroendocrine carcinoma (PNEC) while positive in 86.4% of thymic cases (TNEC). TTF-1 positivity was associated with high sensitivity but low specificity for PNEC, and adding PAX8 negativity significantly increased the specificity. PAX8 positivity alone showed essentially 100% specificity and 86.4% sensitivity for TNEC.
Study suggested that PAX8 eQTLs SNPs (rs4848320 and rs1110839) located in lncRNA PAX8-AS1 might predict decreased risk of cervical cancer.
Pax8 is required for cell proliferation of pronephric precursors and regulates the expression of hnf1b and wnt pathway genes in the kidney field.
nephrogenic transcription factors (osr1, osr2, hnf1b, lhx1, pax8)play important role in nephrogenesis but have no pronephros induction potential upon overexpression; they activate transcription cascades reflecting activation by activin A, retinoic acid
Results show that in both 3- and 8-week-old offspring of the maternal group highly treated with E2, Pax8 was significantly up-regulated in thyroid glands, accompanied by the abnormal CpG island methylation status in the promoter region.
Demonstrate the stepwise emergence of hitherto undescribed, differently Pax2/Pax8- coded anterior and posterior subdomains in the posterior placodal area of mice.
These results suggest that Pax8 maybe the downstream molecule of ALK3, it mediates the murine heart development via cellular senescence, which may serve as a mechanism that compensates for the cell loss via apoptosis in heart development.
Mice lacking microRNAs in Pax8-expressing cells develop hypothyroidism and end-stage renal failure
PAX8 protein expression was associated with germinal layers in human and murine forebrain and hindbrain development.
Pax8 is essential for function and survival of adult thyroid cells.
a core regulatory subcircuit composed of Pax2/8, Gata3 and Lim1 turns on a deeper layer of transcriptional regulators while activating effector genes responsible for cell signaling and tissue organization.
The Pax8 promoter appears to be autoregulated, a feature that might be responsible for the haploinsufficiency displayed by this gene.
Inducible, Pax8-rtTA-based deletion of VHL leads to organ-specific expression of epithelial HIF and erythropoietin in liver and kidney without causing pathological changes.
study concludes that Cadherin-16 is a novel downstream target of the transcription factor Pax8, likely since the early steps of thyroid development, and that its expression is associated with the fully differentiated state of the thyroid cell
Study shows that Pax2;8 double null mice do not develop an ear past the otocyst stage and no sensory and limited neuronal development; these 2 family members are essential for overall ear morphogenesis and sustained neurosensory development.
a thyroid-specific regulatory element in the 5' upstream region of the Pax8 gene
these data identify Pax2 and Pax8 as critical regulators that specify the nephric lineage.
The Box protein Pax-8 gene is an important and cardiac-specific ALK3 downstream gene in the BMP signaling pathway during inter-ventricular septum development.
Pax8(-/-)TRalpha1(-/-) compound mutants die around weaning unless they are substituted with thyroid hormones. Short life span of Pax8(-/-) mice due to complex mechanism involving TRalpha2 and an unliganded TR isoform.
Combination of partial deficiencies in the Titf1 and Pax8 genes results in an overt thyroid dysgenesis phenotype that is absent in either of the singly deficient, heterozygous mice.
Pax8 expression not only in the uterine epithelium of mice but also in the human endometrium. Adequate development of uterus may be affected in congenital hypothyroid female patients with mutations in Pax8 gene.
a crucial role for Pax2 and Pax8 in nephron differentiation and branching morphogenesis of the metanephros.
A 6h exposure to Tg resulted in increases of about 5-fold in TGF-beta1 and PAI-1 mRNA and a decrease of 53% in Pax-8.
Pax2a and Pax8 regulate cell differentiation during sensory placode formation
pax8 works with related genes pax2a/pax2b to downregulate otic expression of foxi1, a necessary step for further otic development
evolutionary links between jaw and ear formation can be traced to Fgf-Foxi1-Pax8 pathways
Pax2a and Pax8 are the main effectors downstream of Fgf signals in ear formation
pax8 is initially required for normal otic induction, and subsequently pax8, pax2a and pax2b act redundantly to maintain otic fate
This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternatively spliced transcript variants encoding different isoforms have been described.
paired box 8
, paired box gene 8
, paired box protein Pax-8
, paired domain gene 8
, Pax-8 protein
, Pax-8 DNA-binding transcription factor