The Relative Activities of the C2GnT1 and ST3Gal-I Glycosyltransferases Determine O-Glycan Structure and Expression of a Tumor-associated Epitope on MUC1

In breast cancer, the O-glycans added to the MUC1 mucin are core 1- rather than core 2-based. We have analyzed whether competition by the glycosyltransferase, ST3Gal-I, which transfers sialic acid to galactose in the core 1 substrate, is key to this switch in MUC1 glycosylation that results in the expression of the cancer-associated SM3 epitope. Of the three enzymes known to convert core 1 to core 2, by the addition of GlcNAc to GalNAc in core1 C2GnT1 is the dominant enzyme expressed in normal breast tissue. Expression of C2GnT1 is low or absent in around 50‥ of breast cancers, whereas expression of ST3Gal-I is consistently increased. Mapping of ST3Gal-I and C2GnT1 within the Golgi pathway showed some overlap. To examine functional competition, the enzymes were overexpressed in T47D cells, which normally make core 1-based structures, have no detectable C2GnT1 activity and express the SM3 epitope. Overexpression of C2GnT1 resulted in loss of binding of SM3 to MUC1, accompanied by a decrease in the GalNAc/GlcNAc ratio, indicative of a switch to core 2 structures. Transfection of a C2GnT1 expressing line with ST3Gal-I restored SM3 binding and reduced GlcNAc incorporation into MUC1O-glycans. Thus, even when C2GnT1 is expressed, theO-glycans added to MUC1 become core 1-dominated structures, provided expression of ST3Gal-I is increased as it is in breast cancer. In breast cancer, the O-glycans added to the MUC1 mucin are core 1- rather than core 2-based. We have analyzed whether competition by the glycosyltransferase, ST3Gal-I, which transfers sialic acid to galactose in the core 1 substrate, is key to this switch in MUC1 glycosylation that results in the expression of the cancer-associated SM3 epitope. Of the three enzymes known to convert core 1 to core 2, by the addition of GlcNAc to GalNAc in core1 C2GnT1 is the dominant enzyme expressed in normal breast tissue. Expression of C2GnT1 is low or absent in around 50‥ of breast cancers, whereas expression of ST3Gal-I is consistently increased. Mapping of ST3Gal-I and C2GnT1 within the Golgi pathway showed some overlap. To examine functional competition, the enzymes were overexpressed in T47D cells, which normally make core 1-based structures, have no detectable C2GnT1 activity and express the SM3 epitope. Overexpression of C2GnT1 resulted in loss of binding of SM3 to MUC1, accompanied by a decrease in the GalNAc/GlcNAc ratio, indicative of a switch to core 2 structures. Transfection of a C2GnT1 expressing line with ST3Gal-I restored SM3 binding and reduced GlcNAc incorporation into MUC1O-glycans. Thus, even when C2GnT1 is expressed, theO-glycans added to MUC1 become core 1-dominated structures, provided expression of ST3Gal-I is increased as it is in breast cancer. UDP-N-acetyl-α-d-N-acetylglucosamine:βGal/αGalNAc-1,6-N-acetylglucosaminyltransferase CMP-Neu5Ac:Galβ1,3GalNAc-α2,3-sialyltransferase peanut agglutinin fetal calf serum fluorescence-activated cell-scanning analysis 4-morpholinepropanesulfonic acid high performance anion exchange chromatography Interest has been focused on the MUC1 mucin as a target antigen for immunotherapy of breast and other carcinomas since the cancer-associated mucin is overexpressed and aberrantly glycosylated (1Taylor-Papadimitriou J. Burchell J. Miles D.W. Dalziel M. Biochim. Biophys. Acta. 1999; 1455: 301-313Crossref PubMed Scopus (428) Google Scholar). The MUC1 mucin is a membrane glycoprotein with an extracellular domain made up largely of tandem repeats of 20 amino acids, each of which contains potential O-glycosylation sites (2Gendler S.J. Lancaster C.A. Taylor-Papadimitriou J. Duhig T. Peat N. Burchell J. Pemberton L. Lalani E.N. Wilson D. J. Biol. Chem. 1990; 268: 3801-3804Google Scholar, 3Gendler S.J. Spicer A.P. Lalani E.N. Duhig T. Peat N. Burchell J. Pemberton L. Boshell M. Taylor-Papadimitriou J. Am. Rev. Resp. Dis. 1991; 144 (suppl. 3): S42-S47Crossref Google Scholar). The aberrant glycosylation has been well documented in breast cancers where it has been shown (4Lloyd K.O. Burchell J. Kudryashov V. Yin B.W.T. Taylor- Papadimitriou J. J. Biol. Chem. 1996; 271: 33325-33334Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar, 5Hanisch F.G. Stadie T.R. Deutzmann F. Peter-Katalinic J. Eur. J. Biochem. 1996; 236: 318-327Crossref PubMed Scopus (122) Google Scholar) that the addition of shorterO-glycans leads to the exposure of peptide epitopes in the tandem repeats, which are normally masked, and the appearance of novel carbohydrate epitopes. Recent data suggest that not only the composition but the number of O-glycans added to MUC1 is altered in breast cancer (6Muller S. Alving K. Peter-Katalinic J. Zachara N. Gooley A.A. Hanisch F.G. J. Biol. Chem. 1999; 274: 18165-18172Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar). Thus, the cancer-associated glycoprotein is antigenically distinct from the normally processed mucins (7Burchell J.M. Taylor-Papadimitriou J. Epithelial Cell Biol. 1993; 2: 155-162PubMed Google Scholar). This difference in antigenic profile is detected by the antibody SM3 (8Burchell J. Gendler S. Taylor-Papadimitriou T. Girling A. Lewis A. Millis R. Lamport D. Cancer Res. 1987; 47: 5476-5482PubMed Google Scholar, 9Girling A. Bartkova J. Burchell J. Gendler S. Gillett C. Taylor-Papadimitriou J. Int. J. Cancer. 1989; 43: 1072-1076Crossref PubMed Scopus (307) Google Scholar), which recognizes a core protein epitope selectively exposed in the tandem repeat of the cancer-associated MUC1 mucin (10Burchell J. Taylor-Papadimitriou J. Boshell M. Gendler S. Duhig T. Int. J. Cancer. 1989; 44: 691-696Crossref PubMed Scopus (215) Google Scholar). Analysis of the O-glycans attached to the mucin produced by the normal lactating breast and by breast cancer cell lines has shown that the oligosaccharides added to the normal mucin are core 2-based structures (11Hanisch F.G. Uhlenbruck G. Peter-Katalinic J. Egge H. Dabrowski J. Dabrowski U. J. Biol. Chem. 1989; 264: 872-883Abstract Full Text PDF PubMed Google Scholar), whereas in the cancer-associated mucin, shorter core 1-based structures dominate (4Lloyd K.O. Burchell J. Kudryashov V. Yin B.W.T. Taylor- Papadimitriou J. J. Biol. Chem. 1996; 271: 33325-33334Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar, 5Hanisch F.G. Stadie T.R. Deutzmann F. Peter-Katalinic J. Eur. J. Biochem. 1996; 236: 318-327Crossref PubMed Scopus (122) Google Scholar, 12Hull S.R. Bright A. Carraway K.L. Abe M. Hayes D.F. Kufe D. Cancer Commun. 1989; 1: 261-267PubMed Google Scholar). As illustrated in Fig.1, core 1 (Galβ1,3GalNAc-Ser/Thr) can be a substrate for enzymes adding GlcNAc in the β1,6 linkage to GalNAc to form core 2 or for sialyltransferases adding sialic acid in α2,3 linkage to galactose. These early steps in O-glycan synthesis are crucial to the final definition of O-glycan structure, since the conversion to core 2 promotes chain branching and elongation, whereas the addition of sialic acid terminates chain growth. In the potential competition of for the core 1 substrate, the of activity of a and in the Golgi pathway to be that are not to Golgi but a S. J. A. C. H. T. J. Cell PubMed Google Scholar). the expression of the ST3Gal-I to a with number C2GnT1 and to with and is in the some expression can be in the Golgi C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). is that are in by that have and expression and are that are to sialic acid in α2,3 linkage to the galactose in core 1 S. 1996; Google Scholar). of the ST3Gal-I to the in the of core 1 structures on MUC1 in as from enzyme and S. J. Biol. Chem. Full Text PDF PubMed Google Scholar, M. T. N. S. PubMed Scopus Google Scholar, M. A. Cancer Res. Google Scholar). the ST3Gal-I enzyme has been to be in breast cancer cell lines and breast cancers C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar, J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). of the O-glycans be by three which of expression in The enzymes C2GnT1 and M. U. S. A. PubMed Scopus Google Scholar, T. G. M. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) only on core 1 to core the other or T. M. G. H. J. Biol. Chem. 1999; 271: Full Text Full Text PDF Scopus Google Scholar, M. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar) is to the of core from core as well as core 2 from core Of the to by it that C2GnT1 is the enzyme expressed in breast and can be expressed the expression of the C2GnT1 enzyme has been to be or absent in breast cancer cell lines J. Burchell J.M. C. Taylor- Papadimitriou J. Eur. J. Biochem. PubMed Scopus Google Scholar, C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar), of the for this enzyme can be in a high of breast cancers J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). This is in to the of expression of ST3Gal-I which is consistently in breast cancers J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). the of expression of the for ST3Gal-I with the of expression of the SM3 epitope and with J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). core 2 branching by is by α2,3 of core 1 in V. H. K.L. M. M. J. 1993; PubMed Scopus Google Scholar, Biochim. Biophys. Acta. 1999; PubMed Scopus Google Scholar, J. PubMed Scopus Google Scholar), it that ST3Gal-I be a key enzyme to mucin core 1 glycosylation in cancer The is whether ST3Gal-I can with C2GnT1 in to an in the of core 2 structures on MUC1 and whether this to exposure of the cancer-associated SM3 epitope. competition to be the enzymes in the of the Golgi We have in the of expression of C2GnT1 the Golgi pathway and this profile with the profile of expression of ST3Gal-I in the Golgi We that the expression of C2GnT1 is in the and ST3Gal-I in the the enzymes overlap. To examine this of is to competition the the C2GnT1 and ST3Gal-I into the breast cancer cell line T47D S. J. M. S. Eur. J. Cancer. Full Text PDF PubMed Scopus Google Scholar). data that the of in the the ST3Gal-I enzyme is to with C2GnT1 for the core 1 substrate in when the is The results that the of the enzymes the of the O-glycans attached to MUC1 and the exposure of the SM3 epitope. Thus, the SM3 epitope exposed in breast cancer expressing the ST3Gal-I enzyme as it is in breast cancer. agglutinin from and were from from from and were from from of the and with MUC1, J. R. Int. J. Scholar, J. Gendler S. Taylor-Papadimitriou T. Girling A. Lewis A. Millis R. Lamport D. Cancer Res. 1987; 47: 5476-5482PubMed Google Scholar) were for antibody the of MUC1 L. Taylor-Papadimitriou J. Gendler S.J. Biochem. Biophys. Res. Commun. PubMed Scopus (122) Google Scholar). The cell line by of normal from J. Bartkova J. K. Lalani E.N. M. S. Taylor-Papadimitriou J. U. S. A. 1991; PubMed Scopus Google Scholar) and in with and The cell line T47D from breast from a S. J. M. S. Eur. J. Cancer. Full Text PDF PubMed Scopus Google Scholar) and in a in 20 breast cancer were provided by Cancer were as with the SM3 as for the cell were in and to a The the C2GnT1 from R. K. of the from to a for The the ST3Gal-I PubMed Scopus Google Scholar) from J. Cancer from a by as a T. M. G. H. J. Biol. Chem. 1999; 271: Full Text Full Text PDF Scopus Google Scholar) a of the expression the from to The T. G. M. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) a the from to The C2GnT1 into the of expressing the Golgi C2GnT1 with epitopes and into the The of and as C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). ST3Gal-I with an epitope the and into the into the cell line were into 2 for to for The cell lines were to and the with a of the in and T47D were with C2GnT1 or with the to the and T47D cell lines expressing and the T47D cell line expressing only the To of and the of a of in the of which the of of cell lines H. C. M. Res. 1996; PubMed Scopus Google Scholar). in the and the in the T47D were into were and were of and cell lines with the ST3Gal-I and C2GnT1 were on a 2 of from of cell line added with and for to for T47D and and for and were for this the to the for for which were and J. Bartkova J. K. Lalani E.N. M. S. Taylor-Papadimitriou J. U. S. A. 1991; PubMed Scopus Google Scholar) were with the C2GnT1 C. of in and Epithelial of Scholar), and were were for 1 in and were with the antibody by to and processed for as by C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). The of the Golgi by to the of antibody to from and by protein to as by C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). were and three in 1 of added to cells, and the were and The of and in cell were as substrate, and the by high performance as by J. Burchell J.M. C. Taylor- Papadimitriou J. Eur. J. Biochem. PubMed Scopus Google Scholar). were expressed as were and in and a of were in of the antibody in or in of as a were in the of and on a were three in were in of in and for in the three in were in of and were analyzed by a analysis of were with or and analyzed for the binding of as (7Burchell J.M. Taylor-Papadimitriou J. Epithelial Cell Biol. 1993; 2: 155-162PubMed Google Scholar). from cell lines or breast as the on in 1 in the and membrane and with with and were for 1 in 2 serum in for 1 and exposed to a and a to around in a were in of and in of were the with an of and the were for for or MUC1 in the in the of MUC1 were analyzed by high performance anion exchange chromatography the glycoprotein with and with the antibody as (4Lloyd K.O. Burchell J. Kudryashov V. Yin B.W.T. Taylor- Papadimitriou J. J. Biol. Chem. 1996; 271: 33325-33334Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar). in were for 2 with reduced to low were and of the with serum and protein The MUC1 with of antibody L. Taylor-Papadimitriou J. Gendler S.J. Biochem. Biophys. Res. Commun. PubMed Scopus (122) Google Scholar), which to the and of the and the by and The in and in 2 acid for and analyzed by on a by with of cell were with or of C. in in a of on a and in a The in serum and with in 20 for 1 with in the for 1 with in 20 of the detected and for three enzymes to core 2 and from core 1 have been M. U. S. A. PubMed Scopus Google Scholar, T. G. M. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, T. M. G. H. J. Biol. Chem. 1999; 271: Full Text Full Text PDF Scopus Google Scholar). Expression of enzymes in the T47D breast cancer cell line and in the by 2 that of enzymes were expressed in T47D cells, whereas C2GnT1 and but not were expressed in from normal breast only C2GnT1 be for the other enzymes for the is shown in of from the cell line 2 of in normal and breast tissue. with C2GnT1 to a of normal for each of the is shown in of of 1 of with C2GnT1 to SM3 breast carcinomas for each of the is shown in of of 1 of In analysis of breast cancers has shown that C2GnT1 breast whereas of are consistently increased J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). the of this for the and enzymes were not To expression of three enzymes in analysis on from 20 breast were as carcinomas and with the SM3 The analysis showed that not expressed in of the the other C2GnT1 to be expressed in of the 20 cancers, the or detectable of were in only of the 20 with other a of of the with the three In an of the in 1 of the expressing of whereas the other low 1 the detected in the only a detectable of This enzyme to be absent from of the 20 with other a Thus, the key enzyme of the core 2 in normal and breast to be expression of is a in breast cancer, the cell line to express this of the normal this line by with which have the T47D cell line not express of the core enzymes but has of ST3Gal-I J. Burchell J.M. C. Taylor- Papadimitriou J. Eur. J. Biochem. PubMed Scopus Google Scholar), it an cell for the of C2GnT1 on O-glycan the C2GnT1 to with the ST3Gal-I enzyme for the core 1 substrate in breast cells, be some in in the Golgi We have shown that the ST3Gal-I is in the of the Golgi C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar), a detectable of expression can be in the The cell line with the ST3Gal-I for the of this enzyme the of the Golgi is well in the of to in has been shown to results for Golgi to that with of enzymes S. J. A. C. H. T. J. Cell PubMed Google Scholar). To whether C2GnT1 with ST3Gal-I, C2GnT1 with epitopes and into To the Golgi an antibody to in glycosylation and that has been to the and the T. M. G. J. Cell Biol. 1993; PubMed Scopus Google Scholar) in not The of C2GnT1 the Golgi by the the Golgi a in C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). This a analysis of the of C2GnT1 the Golgi rather than the Golgi into each as the of than three be into and the of C2GnT1 in with The of C2GnT1 in the early of the to the some expression in the and low but detectable in the Thus, as can be from on the C2GnT1 is than is a of the enzymes that for competition for the core 1 To examine the competition ST3Gal-I and the for the C2GnT1 enzyme into T47D not normally express this and were cell were for and it a activity to that of a cell and it an activity lines in C2GnT1 by not the expression of C2GnT1 as by the activity of in in activity and in MUC1 O-glycans in C2GnT1 GlcNAc of attached to MUC1 produced by the cell in a To for in the of the O-glycans added to MUC1, the cell line and were with and the MUC1 the antibody which with epitopes in the and The of theO-glycans on the mucin as (4Lloyd K.O. Burchell J. Kudryashov V. Yin B.W.T. Taylor- Papadimitriou J. J. Biol. Chem. 1996; 271: 33325-33334Abstract Full Text Full Text PDF PubMed Scopus (315) Google Scholar, C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar), and the results are shown in and As with the T47D cell line and the theO-glycans on MUC1 in the C2GnT1 showed a of This be by the branching and chain that is by the addition of GlcNAc by which is absent in the of MUC1 O-glycans and the of MUC1 with the SM3 a cancer-associated epitope in the tandem repeat of MUC1 (8Burchell J. Gendler S. Taylor-Papadimitriou T. Girling A. Lewis A. Millis R. Lamport D. Cancer Res. 1987; 47: 5476-5482PubMed Google Scholar, 9Girling A. Bartkova J. Burchell J. Gendler S. Gillett C. Taylor-Papadimitriou J. Int. J. Cancer. 1989; 43: 1072-1076Crossref PubMed Scopus (307) Google Scholar), has been (7Burchell J.M. Taylor-Papadimitriou J. Epithelial Cell Biol. 1993; 2: 155-162PubMed Google Scholar, J. M. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). Thus, MUC1 from which core 1 structures, with whereas MUC1 expressed by which core 2-based structures, that when C2GnT1 is expressed in as it is in the T47D cell the epitope by SM3 The of MUC1 from T47D with other and that core protein epitopes in the tandem repeat (10Burchell J. Taylor-Papadimitriou J. Boshell M. Gendler S. Duhig T. Int. J. Cancer. 1989; 44: 691-696Crossref PubMed Scopus (215) Google Scholar) The of the antibody has been shown to be reduced but not when theO-glycans added to MUC1 are core 2-based (7Burchell J.M. Taylor-Papadimitriou J. Epithelial Cell Biol. 1993; 2: 155-162PubMed Google Scholar). the other the antibody well with MUC1 core (7Burchell J.M. Taylor-Papadimitriou J. Epithelial Cell Biol. 1993; 2: 155-162PubMed Google Scholar). as the of with MUC1 produced by the cell line is whereas is largely the for the high expressing but a in the binding of SM3 and is with of in the cell that the of MUC1 expression is The data of and that the C2GnT1 enzyme can the glycosylation of T47D cells, to chain and of the SM3 epitope and a in the expression of the epitope. This be from the that the C2GnT1 enzyme has to the core 1 substrate it to the the other have that some breast cancers and breast cancer cell lines express the C2GnT1 but the SM3 epitope is not C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar, J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). Analysis by in showed that of the breast cancers express increased of the ST3Gal-I the of expression of ST3Gal-I to with J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). the in expression of the for has been shown to be accompanied by an in the of protein analysis with a antibody to this J. M. J. and H. in To whether increased expression of ST3Gal-I can with C2GnT1 for the core 1 substrate in breast cancer cells, for ST3Gal-I with the into the core cell lines and The were analyzed for and for attached to MUC1, and for expression of the SM3 epitope. the of of and for from the cell line with the of with The core 1 activity in cell other enzymes the core activity other enzymes this the with the of ST3Gal-I and it is that the are ST3Gal-I and the the of expression of ST3Gal-I showed a high of expression of for this enzyme not the ST3Gal-I is functional in in core 1 structures is shown by the loss of of the with peanut for in in core 1 to the activity of enzymes core 2 from core to the activity of cell adding sialic acid to core activity to the activity in cell adding GlcNAc to core 1 on the GalNAc SM3 to the activity of cell adding sialic acid to core activity to the activity in cell adding GlcNAc to core 1 on the GalNAc in a can be from that of the SM3 epitope with the expression of activity in The analysis of antibody is shown in for with the and T47D cell whereas expression of the MUC1 epitopes by SM3 and are in the expressing of expression is increased in cells, where the of ST3Gal-I activity to C2GnT1 activity is In to the results with the cell of the ST3Gal-I of the high C2GnT1 showed of the SM3 epitope by analysis not The appearance of the SM3 epitope accompanied by in the composition of the O-glycans attached to Thus, analysis of the in O-glycans attached to MUC1 from a decrease in the of GlcNAc to GalNAc with as in in the only pathway to chain from core 1 is core 2, the results that ST3Gal-I can with C2GnT1 for the core 1 The O-glycans added in are by adding and as the the Golgi This the in the enzymes that the substrate but can for the C2GnT1 and ST3Gal-I, of which can core 1 as a substrate, to be in the final of the O-glycans added to MUC1 in breast cancer, since chain and chain it be that detected in a number of breast carcinomas C2GnT1 to be the dominant core 2 in normal and from the data showed that ST3Gal-I is in the with detectable in the C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). We that in cells, C2GnT1 is in the but with some expression in the and low but detectable in the This is in with other have C2GnT1 to be in the of D. R. A. M. D. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). To whether the of is to competition the have of a breast cancer cell line T47D that of expression of C2GnT1 and To competition the in O-glycan composition were by the of the GalNAc and GlcNAc in MUC1 be that have shown a decrease in the of GlcNAc to GalNAc in MUC1 O-glycans in with ST3Gal-I C. Burchell J. S. K.O. Taylor-Papadimitriou J. J. Cell Biol. PubMed Scopus Google Scholar). this cell line activity not only of core enzymes but of the which GlcNAc to the in core 1 J. Burchell J.M. C. Taylor- Papadimitriou J. Eur. J. Biochem. PubMed Scopus Google Scholar). the ST3Gal-I enzyme be with this activity or with T47D cells, not express of enzymes J. Burchell J.M. C. Taylor- Papadimitriou J. Eur. J. Biochem. PubMed Scopus Google this the in the GlcNAc to GalNAc in the T47D can be to competition the ST3Gal-I and C2GnT1 Thus, even the for that the of C2GnT1 is than the of the ST3Gal-I enzyme in the Golgi when ST3Gal-I activity is this pathway the in the competition the enzymes analyzed from the that ST3Gal-I activity to be consistently whereas the of C2GnT1 activity not reduced in breast a the of expression of ST3Gal-I and the SM3 epitope J.M. R. A. C. L. H. Miles D. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). In this that SM3 and to MUC1 is on the of C2GnT1 and The results are with the that in breast cancers, where the of ST3Gal-I are competition with C2GnT1 is in a reduced of GlcNAc in theO-glycans attached to the cancer mucin and exposure of the SM3 epitope. is of to that even in the expressing the the SM3 epitope that the ST3Gal-I enzyme can with this core in ST3Gal-I and the expressed in cells, which be the enzyme T. G. M. H. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), has been D. N. M. Full Text Full Text PDF PubMed Scopus Google Scholar). These in ST3Gal-I to that the of the O-glycans on as on has a on the and of the increased expression of ST3Gal-I, which have in breast cancers, by cell is core 1 a sialic acid in α2,3 linkage is a for and MUC1 well with this sialic acid binding protein on which can be as in a of breast cancers D. A. L. Miles D.W. Burchell J. Taylor-Papadimitriou J. 1999; PubMed Scopus Google Scholar). The of C2GnT1 activity on MUC1 glycosylation has been in a cell line where the SM3 epitope J. M. J. Biol. Chem. 1999; 274: Full Text Full Text PDF PubMed Scopus Google Scholar). The loss of the SM3 binding to MUC1 is to the core 2 the by SM3 (10Burchell J. Taylor-Papadimitriou J. Boshell M. Gendler S. Duhig T. Int. J. Cancer. 1989; 44: 691-696Crossref PubMed Scopus (215) Google Scholar). This by the core 2 of to the of the MUC1 the in number of O-glycans attached to MUC1 in normal with T47D (6Muller S. Alving K. Peter-Katalinic J. Zachara N. Gooley A.A. Hanisch F.G. J. Biol. Chem. 1999; 274: 18165-18172Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar). In this for the GalNAc adding the to and be In have that ST3Gal-I can with C2GnT1 in core synthesis on MUC1 in breast cancer. We that it is the of ST3Gal-I in breast cancer that leads to the dominant expression of core 1 O-glycans on MUC1 in this We and for in the and enzyme and Cancer and of for of ST3Gal-I and C2GnT1 We for the

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