Identification of a Third EXT-like Gene (EXTL3) Belonging to the EXT Gene Family

Hul, Wim Van; Wuyts, Wim; Hendrickx, Jan; Speleman, Frank; Wauters, J.; Boulle, Kristel De; Roy, Nadine Van; Bossuyt, P.; Willems, Patrick J.

doi:10.1006/geno.1997.5101

Cited by 122 publications

(81 citation statements)

References 30 publications

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“…EXTL3 (clone yy17e02), the third EXT-like gene (Van Hul et al, 1998) belongs to the family of genes involved in hereditary multiple exostoses (EXT) that may represent a class of tumor suppressors (McCormick et al, 1998). Our data show that this gene is underexpressed in three sporadic breast tumors compared to normal tissue (Figure 2c).…”

mentioning

confidence: 73%

Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes

Ugolini¹,

et al. 1999

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Deletions and ampli®cations are frequent alterations of the short arm of chromosome 8 associated with various types of cancers, including breast cancers. This indicates the likely presence of tumor suppressor genes and oncogenes. In the present study, we have used the expressed sequence tag (EST) map of 8p11-21 to assemble a set of available cDNAs representing genes from this region. DNA arrays were prepared for expression analysis and search for genes potentially involved in breast cancer. Underexpresion in tumoral breast cells (versus normal breast) was observed for 15 transcripts. Among these, the Frizzled-related gene FRP1/FRZB, was turned o in 78% of breast carcinomas, suggesting that the lack of its product may be associated with malignant transformation. Overexpression in tumoral breast cells was observed for 13 genes. The FGFR1 gene, that encodes a tyrosine kinase receptor for members of the ®broblast growth factor family, was identi®ed as a good candidate for one ampli®cation unit. Taken together, our results demonstrate that such a strategy can rapidly identify genes with an altered pattern of expression and provide candidate genes for malignancies.

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mentioning

confidence: 73%

Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes

Ugolini¹,

et al. 1999

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“…However, three EXT-like genes homologous to EXT genes have been isolated: EXTL1, EXTL2͞EXTR2, and EXTL3͞ EXTR1 (20)(21)(22)(23). Their chromosomal locations imply that they also might be tumor suppressors (20,21,24,25), although they are not linked with HME.…”

Section: H Eparan Sulfate (Hs) Is a Glycosaminoglycan (Gag) Foundmentioning

confidence: 99%

Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode α1,4- N -acetylglucosaminyltransferases that likely are involved in heparan sulfate/ heparin biosynthesis

Kim

Kitagawa

Tamura

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

156

144

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The tumor suppressors EXT1 and EXT2 are associated with hereditary multiple exostoses and encode bifunctional glycosyltransferases essential for chain polymerization of heparan sulfate (HS) and its analog, heparin (Hep). Three highly homologous EXT-like genes, EXTL1-EXTL3, have been cloned, and EXTL2 is an ␣1,4-GlcNAc transferase I, the key enzyme that initiates the HS͞Hep synthesis. In the present study, truncated forms of EXTL1 and EXTL3, lacking the putative NH 2-terminal transmembrane and cytoplasmic domains, were transiently expressed in COS-1 cells and found to harbor ␣-GlcNAc transferase activity. EXTL3 used not only N-acetylheparosan oligosaccharides that represent growing HS chains but also GlcA␤1-3Gal␤1-O-C 2H4NH-benzyloxycarbonyl (Cbz), a synthetic substrate for ␣-GlcNAc transferase I that determines and initiates HS͞Hep synthesis. In contrast, EXTL1 used only the former acceptor. Neither EXTL1 nor EXTL3 showed any glucuronyltransferase activity as examined with N-acetylheparosan oligosaccharides. Heparitinase I digestion of each transferase-reaction product showed that GlcNAc had been transferred exclusively through an ␣1,4-configuration. Hence, EXTL3 most likely is involved in both chain initiation and elongation, whereas EXTL1 possibly is involved only in the chain elongation of HS and, maybe, Hep as well. Thus, their acceptor specificities of the five family members are overlapping but distinct from each other, except for EXT1 and EXT2 with the same specificity. It now has been clarified that all of the five cloned human EXT gene family proteins harbor glycosyltransferase activities, which probably contribute to the synthesis of HS and Hep.

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“…15 The EXT genes are members of a larger family of homologous genes which also currently includes three EXT-like genes -EXTL1, 16 EXTL2 17 and EXTL3. 18 Recently it has been shown that the EXT1 and EXT2 genes are glycosyltransferases required for the biosynthesis of heparan sulfate. 19,20 The recent identification of the tout-velu (ttv) gene, the Drosophila homologue of the EXT1 gene which is essential for proper diffusion of the Drosophila hedgehog (Hh) protein, 21 suggests that EXT1 is probably involved in the synthesis of a GAG that specifically interacts with Hh protein at the cell surface.…”

Section: Introductionmentioning

confidence: 99%

Molecular and clinical examination of an Italian DEFECT 11 family

et al. 1999

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The DEFECT 11 syndrome is a contiguous gene syndrome associated with deletions in the proximal part of chromosome 11p. In this study, we describe in an Italian family the co-existence of multiple exostoses (EXT) and enlarged parietal foramina (FPP), the two major symptoms of this syndrome, with abnormalities of the central nervous system. The latter may be a yet undescribed feature of DEFECT 11 syndrome. FISH and molecular analysis allowed us to identify a small deletion on 11p11-p12, further refining the localisation of the FPP gene involved in the DEFECT 11 syndrome.

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Identification of a Third EXT-like Gene (EXTL3) Belonging to the EXT Gene Family

Cited by 122 publications

References 30 publications

Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes

Differential expression assay of chromosome arm 8p genes identifies Frizzled-related (FRP1/FRZB) and Fibroblast Growth Factor Receptor 1 (FGFR1) as candidate breast cancer genes

Human tumor suppressor EXT gene family members EXTL1 and EXTL3 encode α1,4- N -acetylglucosaminyltransferases that likely are involved in heparan sulfate/ heparin biosynthesis

Molecular and clinical examination of an Italian DEFECT 11 family

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