Miyahara, N. et al., Sutherlin, M.E. et al., Bennett, E.P. et al., Kristiansen, O.P. et al., Topaz, O. et al., et al.
Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis .
IDDM7 links to insulin-dependent diabetes mellitus in Danish multiplex families but linkage is not explained by novel polymorphisms in the candidate gene GALNT3. The Danish Study Group of Diabetes in Childhood and The Danish IDDM Epidemiology and Genetics Group .
Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3 .
RESULTS: The expression levels of GalNAc-T3 protein and mRNA were increased in gallbladder carcinomas compared with the levels in adjacent noncancerous tissues and in intact gallbladders .
The low expression of GalNAc-T3 was associated with poorly differentiated tumour (P<0.0001), poor pathologic stage (P<0.0001), lymph node metastasis (P<0.0001), and tumour recurrence (P=0.016) .
This region includes the gene GALNT3, which encodes a glycosyltransferase responsible for initiating mucin-type O-glycosylation .
Sequence analysis of GALNT3 identified biallelic deleterious mutations in all individuals with FTC, suggesting that defective post-translational modification underlies the disease .
HFTC was recently shown to result from mutations in two different genes: GALNT3, which codes for a glycosyltransferase, and FGF23, which codes for a potent phosphaturic protein .
We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma .
Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting .
The genomic organizations of GALNT3 and GALNT6 are identical with the coding regions placed in 10 exons, but the genes are localized differently at 2q31 and 12q13, respectively .
Acceptor substrate specificities of GalNAc-T3 and -T6 were similar and different from other GalNAc-transferases .
GalNAc-T6 exhibited high sequence similarity to GalNAc-T3 throughout the coding region, in contrast to the limited similarity that exists between homologous glycosyltransferase genes, which is usually restricted to the putative catalytic domain .
Decreasing the expression of the GALNT3 gene by RNA interference resulted in enhanced processing of FGF23 .
Conclusions: Our findings demonstrate that GALNT3 inactivation in patients with TC leads to inadequate production of biologically active FGF23 as the most likely cause of the hyperphosphatemic phenotype .
GalNAc-T3 was distributed throughout the entire ocular surface epithelium, whereas GalNAc-T1 was found in scattered cells in conjunctiva only .
For example, GalNAc-T1 and -T2 but not -T3 were highly expressed in WI38 cells, and GalNAc-T3 but not GalNAc-T1 or -T2 was expressed in spermatozoa .
CONCLUSIONS: The high testicular expression of GALNT3 suggests that the gene alteration could act locally by causing deposition of calcium, and the testis may be an underestimated site of calcification in FTC .
Postsurgical survival was significantly poorer in cases showing diffuse-type localization than in those showing granular-type localization (P = 0.033) CONCLUSIONS: In pT(2) gallbladder carcinoma, the presence of diffuse-type localization of GalNAc-T3 in the subserosal layer is correlated with aggressiveness of the disease .
We found that normal bronchial epithelial cells, bronchial gland cells, and alveolar pneumocytes showed cytoplasmic immunostaining for GalNAc-T3 .
The overall amino acid sequence similarity with GalNAc-T1 and -T2 is approximately 45%; 12 cysteine residues that are shared between GalNAc-T1 and -T2 are also found in GalNAc-T3 .
The UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyltransferase isozyme 3 (GalNAc-T3) has the epithelial gland-specific expression and catalyzes mucin-type O-glycosylation .
OBJECTIVE: UDP-N-acetyl-alpha-D-galactosamine-polypeptide N-acetylgalactosaminyl transferase-3 (GalNAc-T3) regulates the initial glycosylation of mucin-type O-linked proteins .
HFTC was shown recently to result from mutations in two genes: GALNT3, coding for a glycosyltransferase responsible for initiating O-glycosylation, and FGF23, coding for a potent phosphaturic protein .
Hence, it is unlikely that the GALNT3 is an IDDM susceptibility gene .
GALNT3 that encodes the UDP-GalNAc: polypeptide N-acetyl-galactosaminyltransferase-T3 (GalNAc-T3), was recently identified and mapped to a region 5-25 cM from D2S152 .
Moreover, tumours losing GalNAc-T3 expression had a significantly higher Ki-67 labelling index than tumours retaining GalNAc-T3 expression (P=0.0003) .
Transient transfection of plasmids containing a reporter gene under the control of GalNAc-T3 indicated that several transcriptional elements are involved in response to sodium butyrate, with the nuclear respiratory factor-1 (NRF-1)-binding motif located between -88 and -77nt being the most important .
Objective: The objective was to identify mutations in FGF23 or GALNT3 responsible for a mild TC phenotype by DNA sequencing and to determine serum FGF23 levels by ELISA .
Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis .
In this study, immunohistochemistry was performed to determine the expression level of GalNAc-T3 in 34 cases of pT(2) gallbladder carcinoma to determine the correlation of the GalNAc-T3 expression level with mode of recurrence and postsurgical survival .
METHODS: Using the specific antibody, we evaluated the expression of GalNAc-T3 in 125 early gastric cancers that were treated as classical gastrectomy with lymphadenectomy, and analyzed the relationship between the expression of GalNAc-T3 and clinicopathological features .
Real-time quantitative PCR analysis across 21 PCa and 34 BPH tissues showed 4.6-fold overexpression of GalNAc-T3 (p = 0.005) .