Biomedical subjects

Diana Blaydon

Publications and source records attributed to Diana Blaydon.

3 recordsLinked to original sources

PubMed2007

Role for WNT16B in human epidermal keratinocyte proliferation and differentiation.

WNT signalling regulates a variety of cell functions including cell fate, polarity, and differentiation via the canonical or beta-catenin stabilisation pathway and/or the planar cell polarity or non-canonical pathway. We have previously demonstrated that two isoforms (A and B) from the WNT16 locus have differential expression in various adult human tissues. In this study we show that WNT16B but not WNT16A isoform was upregulated in basal cell carcinomas compared with normal skin. We further investigated the cellular and molecular functions of WNT16B in primary human epidermal keratinocytes and a keratinocyte cell line. Cellular expression of WNT16B neither stabilised beta-catenin nor activated the lymphoid enhancer factor or T-cell factor transcriptional reporter in primary keratinocytes. WNT16B activated the Jun-N-terminal kinase cascade suggesting the activation of a non-canonical WNT signalling pathway. Constitutive expression of WNT16B significantly enhanced the rate of cell proliferation and prolonged clonogenicity in primary keratinocytes. Silencing WNT16B by RNA interference reduced keratinocyte proliferation. Furthermore, overexpression of WNT16B induced a hyperproliferation phenotype in an organotypical culture system. This work presents the first evidence that WNT16B activates human keratinocyte proliferation possibly via a beta-catenin-independent non-canonical WNT transduction pathway.

Adenosine Triphosphate↗

PubMed2005

Genomewide single nucleotide polymorphism microarray mapping in basal cell carcinomas unveils uniparental disomy as a key somatic event.

Basal cell carcinoma is the most common human cancer with increasing incidence reported worldwide. Despite the aberrant signaling role of the Hedgehog pathway, little is known about the genetic mechanisms underlying basal cell carcinomas. Towards a better understanding of global genetic events, we have employed the Affymetrix Mapping 10K single nucleotide polymorphism (SNP) microarray technique for "fingerprinting" genomewide allelic imbalance in 14 basal cell carcinoma-blood pair samples. This rapid high-resolution SNP genotyping technique has revealed a somatic recombination event-uniparental disomy, leading to a loss of heterozygosity (LOH), as a key alternative genetic mechanism to allelic imbalances in basal cell carcinomas. A highly conserved LOH region at 9q21-q31 was found in 13 of 14 (93%) basal cell carcinomas. Further statistical and fluorescence in situ hybridization analyses confirmed that the 9q LOH was a result of uniparental disomy in 5 of 13 (38%) basal cell carcinomas. De novo mutations in the Patched 1 gene (PTCH) were found in 9 of 13 (69%) basal cell carcinomas with 9q LOH. A second important locus, containing LOH at 6q23-q27 was found in 5 of 14 (36%) basal cell carcinomas, suggesting that the presence of an additional putative tumor suppressor gene may be contributing to basal cell carcinoma development. This study shows that the rate of 9q LOH in basal cell carcinomas has been previously underestimated. Furthermore, we provide the first evidence that uniparental disomy due to somatic recombination constitutes one of the mechanisms of LOH in basal cell carcinoma tumorigenesis.

Aged↗

PubMed2004

Infantile hyperinsulinism associated with enteropathy, deafness and renal tubulopathy: clinical manifestations of a syndrome caused by a contiguous gene deletion located on chromosome 11p.

We describe the clinical features of a new syndrome causing hyperinsulinism in infancy (HI), severe enteropathy, profound sensorineural deafness, and renal tubulopathy in three children born to two pairs of consanguineous parents. This combination of clinical features is explained by a 122-kb contiguous gene deletion on the short arm of chromosome 11. It deletes 22 of the 39 exons of the gene coding for the SUR1 component of the KATP channel on the pancreatic beta-cell thereby causing severe HI. It also deletes all but two of the 28 exons of the USH1C gene, which causes Usher syndrome and is important for the normal development and function of the ear and the eye, the gastrointestinal tract, and the kidney, thereby accounting for the symptoms of deafness, vestibular dysfunction and retinal dystrophy seen in type 1 Usher syndrome, diarrhoea, malabsorption, and tubulopathy. This contiguous gene deletion provides important insights into the normal development of several body organ systems.

Child, Preschool↗