Mammalian Sulf1 RNA alternative splicing and its significance to tumour growth regulation
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SULF1/SULF2 enzymes regulate the activities of several growth factors by selective hydrolysis of 6-O-sulphates of heparan sulphate proteoglycan co-receptors, the sulfation of which is essential for signal transduction of some ligand/receptor interactions but not others. This study demonstrates the existence of SULF1 variants with a wide spectrum of splicing patterns in mammalian tumours. The levels and relative proportions of SULF1/SULF2 splice variants markedly vary in different tumours with a potential to regulate cell growth differentially. Although mammalian Sulf1 compared with Sulf2 gene generates a much larger number of splice variants, both enzymes follow generally similar distribution and signalling association trends in hepatocellular carcinomas.
KeywordsSulf1 splice variants Sulf2 variants Tumour growth Hepatocellular carcinoma Cell signalling
We thank ARC and the Wellcome Trust for the financial support of some sections of this work through a project grant and some vacation studentships. We would also like to thank Dr. Steve Allen for his critical reading of the manuscript. The human embryonic and fetal material was provided by the Joint MRC grant G0700089 and Wellcome Trust grant GR082557 through Human Developmental Biology Resource, ICH, UCL.
- 13.Dhoot G. Recent progress and related patents on the applications of SULF1/SULF2 enzymes in regenerative medicine and cancer therapies. Recent Pat Regen Med. 2012;2:137–45.Google Scholar
- 14.Lai JP, Chien JR, Moser DR, Staub JK, Aderca I, Montoya DP, Matthews TA, Nagorney DM, Cunningham JM, Smith DI, Greene EL, Shridhar V, Roberts LR. Hsulf1 sulfatase promotes apoptosis of hepatocellular cancer cells by decreasing heparin-binding growth factor signaling. Gastroenterology. 2004;126:231–48.CrossRefPubMedGoogle Scholar
- 15.Lai JP, Sandhu DS, Yu C, Han T, Moser CD, Jackson KK, Guerrero RB, Aderca I, Isomoto H, Garrity-Park MM, Zou H, Shire AM, Nagorney DM, Sanderson SO, Adjei AA, Lee JS, Thorgeirsson SS, Roberts LR. Sulfatase 2 up-regulates glypican 3, promotes fibroblast growth factor signaling, and decreases survival in hepatocellular carcinoma. Hepatology. 2008;47:1211–22.CrossRefPubMedPubMedCentralGoogle Scholar
- 16.Yang JD, Sun Z, Hu C, Lai J, Dove R, Nakamura I, Lee JS, Thorgeirsson SS, Kang KJ, Chu IS, Roberts LR. Sulfatase 1 and sulfatase 2 in hepatocellular carcinoma: associated signaling pathways, tumor phenotypes, and survival. Genes Chromosomes Cancer. 2011;50:122–35.CrossRefPubMedPubMedCentralGoogle Scholar