Bladder exstrophy-epispadias complex (BEEC) is a complex and debilitating congenital disease. Familial and twin studies suggest a possible genetic component in BEEC pathogenesis. Bladder mesenchyme (detrusor) development requires induction by a signal from bladder urothelium, and we and others have shown the Shh-Gli-Bmp4 signalling pathway is likely to be involved. P63 is a master regulator in epithelial stratification and is expressed in urothelium. We have shown that p63 knock-out mice undergo excessive urothelial apoptosis. Failure of mesenchymal induction by epithelium leads to BEEC. We further demonstrated that insertion/deletion (in/del) polymorphisms (1 base pair (bp) ins and 4 bp ins., and 12 bp del) in the ΔNP63 promoter reduce transcriptional efficiency, and are associated with a statistically significant increase in the risk of BEEC in humans. Furthermore, a Genome-Wide Expression Profiling (GWEP) study suggests possible involvement of PERP in human BEEC. Intriguingly, PERP is a direct target of p63 during development, and is also involved in epithelial stratification. PERP co-localizes with desmosome, and both PERP and desmosome are essential for maintaining tissue integrity by cellular adhesion and epithelial stratification. A recent study showed that PERP and desmosome expression levels are abnormal in human BEEC patients. This review describes the role of the P63 > PERP > desmosome pathway in the development of human bladder during embryogenesis. We hypothesize that disruption of this pathway may increase the risk of BEEC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.jpurol.2013.05.001 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Human keratinocytes grown at a gas-permeable interface in vitro stratify correctly to generate engineered human epidermis.
Cytotherapy
December 2024
School of Biological Sciences, University of Auckland, Auckland, New Zealand; Maurice Wilkins Centre, The University of Auckland, Auckland, New Zealand. Electronic address:
Background: One of the key functions of human skin is to provide a barrier, protecting the body from the surrounding environment and maintaining homeostasis of the internal environment. A mature, stratified epidermis is critical to achieve skin barrier function and is particularly important when producing skin grafts in vitro for wound treatment. For decades epidermal stratification has been achieved in vitro by culturing keratinocytes at an air-liquid interface, triggering proliferating basal keratinocytes to differentiate and form all epidermal layers.
View Article and Find Full Text PDFClinical significance of stratifying prostate cancer patients through specific circulating genes.
Mol Oncol
January 2025
Urologic Oncology Research Group, Cancer Research Program, Research Institute of the McGill University Health Center, Montreal, Canada.
Patient stratification remains a challenge for optimal treatment of prostate cancer (PCa). This clinical heterogeneity implies intra-tumoural heterogeneity, with different prostate epithelial cell subtypes not all targeted by current treatments. We reported that such cell subtypes are traceable in liquid biopsies through representative transcripts.
View Article and Find Full Text PDFOpportunities for predictive proteogenomic biomarkers of drug treatment sensitivity in epithelial ovarian cancer.
Front Oncol
January 2025
Department of Laboratory Medicine and Pathology, University of Minnesota School of Medicine, Minneapolis, MN, United States.
Genomic analysis has played a significant role in the identification of driver mutations that are linked to disease progression and response to drug treatment in ovarian cancer. A prominent example is the stratification of epithelial ovarian cancer (EOC) patients with homologous recombination deficiency (HRD) characterized by mutations in DNA damage repair genes such as for treatment with PARP inhibitors. However, recent studies have shown that some epithelial ovarian tumors respond to PARP inhibitors irrespective of their HRD or mutation status.
View Article and Find Full Text PDFDevelopment and experimental validation of a senescence-related long non-coding RNA signature for prognostic prediction and immune microenvironment characterization in gastric cancer patients.
J Gastrointest Oncol
December 2024
Department of Gastroenterological Surgery and Hernia Center, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Background: Cellular senescence is considered a new marker of cancer. It has been suggested that long non-coding RNA (lncRNA) can be used to predict the prognosis of cancers. However, it remains to be seen whether the lncRNAs associated with cellular senescence can be used to predict the prognosis of gastric cancer (GC).
View Article and Find Full Text PDFSialoblastomas With Solid Pattern Have FGFR2 Mutations and an Unfavorable Prognosis.
Am J Surg Pathol
January 2025
Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai.
Although sialoblastoma (SBL) is defined as a low-grade malignant salivary gland anlage neoplasm in the 2022 World Health Organization (WHO) Classification of Head and Neck Tumors, its histology, genetics, and behavior remain controversial due to the rarity of the tumor. Here, we performed the first comprehensive clinical, histologic, and molecular analyses of 8 SBLs to better understand their pathogenesis and prognosis. This cohort consisted of 5 boys and 3 girls, with ages ranging from birth to 9 years at diagnosis.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!