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Cytokeratin 15 marks basal epithelia in developing ureters and is upregulated in a subset of urothelial cell carcinomas.
- Source :
-
PloS one [PLoS One] 2013 Nov 18; Vol. 8 (11), pp. e81167. Date of Electronic Publication: 2013 Nov 18 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- The mammalian ureter contains a water-tight epithelium surrounded by smooth muscle. Key molecules have been defined which regulate ureteric bud initiation and drive the differentiation of ureteric mesenchyme into peristaltic smooth muscle. Less is known about mechanisms underlying the developmental patterning of the multilayered epithelium characterising the mature ureter. In skin, which also contains a multilayered epithelium, cytokeratin 15 (CK15), an acidic intermediate filament protein, marks cells whose progeny contribute to epidermal regeneration following wounding. Moreover, CK15+ precursor cells in skin can give rise to basal cell carcinomas. In the current study, using transcriptome microarrays of embryonic wild type mouse ureters, Krt15, coding for CK15, was detected. Quantitative polymerase chain reaction analyses confirmed the initial finding and demonstrated that Krt15 levels increased during the fetal period when the ureteric epithelium becomes multilayered. CK15 protein was undetectable in the ureteric bud, the rudiment from which the ureter grows. Nevertheless, later in fetal development, CK15 was immunodetected in a subset of basal urothelial cells in the ureteric stalk. Superficial epithelial cells, including those positive for the differentiation marker uroplakin III, were CK15-. Transformation-related protein 63 (P63) has been implicated in epithelial differentiation in murine fetal urinary bladders. In wild type fetal ureters, CK15+ cells were positive for P63, and p63 homozygous null mutant ureters lacked CK15+ cells. In these mutant ureters, sections of the urothelium were monolayered versus the uniform multilayering found in wild type littermates. Human urothelial cell carcinomas account for considerable morbidity and mortality. CK15 was upregulated in a subset of invasive ureteric and urinary bladder cancers. Thus, in ureter development, the absence of CK15 is associated with a structurally simplified urothelium whereas, postnatally, increased CK15 levels feature in malignant urothelial overgrowth. CK15 may be a novel marker for urinary tract epithelial precursor cells.
- Subjects :
- Aged
Animals
Carcinoma, Basal Cell metabolism
Carcinoma, Basal Cell pathology
Cell Differentiation
Embryo, Mammalian
Epithelial Cells pathology
Female
Fetus
Gene Expression Regulation, Developmental
Homozygote
Humans
Keratin-15 metabolism
Male
Mice
Middle Aged
Morphogenesis genetics
Phosphoproteins genetics
Phosphoproteins metabolism
Tissue Array Analysis
Trans-Activators genetics
Trans-Activators metabolism
Transcriptome
Ureter cytology
Ureter embryology
Urinary Bladder Neoplasms metabolism
Urinary Bladder Neoplasms pathology
Uroplakin III genetics
Uroplakin III metabolism
Urothelium pathology
Carcinoma, Basal Cell genetics
Epithelial Cells metabolism
Gene Expression Regulation, Neoplastic
Keratin-15 genetics
Ureter metabolism
Urinary Bladder Neoplasms genetics
Urothelium metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24260555
- Full Text :
- https://doi.org/10.1371/journal.pone.0081167