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Journal ArticleDOI

Expression of M-N#1, a histo-blood group B–like antigen, is strongly up-regulated in nonapoptosing mammary epithelial cells during rat mammary gland involution

01 Jun 2001-Glycobiology (Oxford University Press)-Vol. 11, Iss: 6, pp 441-449
TL;DR: It is shown that up-regulation of carbohydrate antigens is not a general phenomenon during mammary gland involution, and thus that M-N#1 antigen expression is specifically regulated, and that alpha(1,2)fucosyltransferase A, an enzyme required for M-M-N-1 antigen synthesis, is at least partly responsible for regulated M- N# 1 antigen expression postlactation.
Abstract: Antibodies against the histo-blood group B–like antigen M-N#1 efficiently block the growth in vivo of rat mammary carcinoma cells that bear the antigen (Sleeman et al., 1999, Oncogene 18, 4485–4494). To try to understand the function of the M-N#1 antigen, we investigated when and where the antigen is expressed during the normal function of the rat mammary gland. Expression was virtually only seen during mammary gland involution. Here, strong expression of the antigen was observed in mammary epithelial cells, beginning around 2 days postweaning and lasting throughout the involution process. Dexamethasone treatment of animals postlactation inhibited alveolar collapse and remodeling in the mammary gland but inhibited neither the apoptosis of mammary epithelial cells nor the expression of the M-N#1 antigen. We show that up-regulation of carbohydrate antigens is not a general phenomenon during mammary gland involution, and thus that M-N#1 antigen expression is specifically regulated. Up-regulation of α(1,2)fucosyltransferase A, an enzyme required for M-N#1 antigen synthesis, is at least partly responsible for regulated M-N#1 antigen expression postlactation. Most significantly, we observed that the M-N#1 antigen is virtually exclusively expressed on nonapoptosing epithelial cells in the involuting mammary gland. These data suggest that M-N#1 antigen expression might either provide a survival function and/or be expressed in epithelial cells that are destined to grow and remodel mammary duct structures.

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Citations
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Journal ArticleDOI
TL;DR: A polymeric conjugate is synthesized in such a way that de-N-acetylated A-trisaccharide is attached to a polymer via the nitrogen in position C-2 of the galactosamine residue, in order to test the hypothesis that the supposed AB-epitope should be situated in the part of the molecule that is opposite to the NHAc group of GalNAc residue.
Abstract: Although the nature of the blood groups A and B has been comprehensively studied for a long time, it is still unclear as to what exactly is the epitope that is recognized by antibodies having AB specificity, i.e. monoclonal and polyclonal antibodies which are capable of interacting equally well with the antigens GalNAcalpha 1-3(Fucalpha 1-2)Gal (A trisaccharide) and Galalpha 1-3(Fucalpha 1-2)Gal (B trisaccharide), but do not react with their common fragment Fucalpha 1-2Gal. We have supposed that besides Fucalpha 1-2Gal, A and B antigens have one more shared epitope. The trisaccharides A and B are practically identical from the conformational point of view, the only difference being situated at position 2 of Galalpha residue, i.e. trisaccharide A has a NHAc group, whereas trisaccharide B has a hydroxyl group (see formulas). We have hypothesized that the AB-epitope should be situated in the part of the molecule that is opposite to the NHAc group of GalNAc residue. In order to test this hypothesis we have synthesized a polymeric conjugate in such a way that de-N-acetylated A-trisaccharide is attached to a polymer via the nitrogen in position C-2 of the galactosamine residue. In this conjugate the supposed AB-epitope should be maximally accessible for antibodies from the solution, whereas the discrimination site of antigens A and B by the antibodies should be maximally hidden due to the close proximity of the polymer. Interaction with several anti-AB monoclonal antibodies revealed that a part of them really interacted with the synthetic AB-glycotope, thus confirming our hypothesis. Moreover, similar antibodies were revealed in the blood of healthy blood group 0 donors. Analysis of spatial models was performed in addition to identify the hydroxyl groups of Fuc, Galalpha, and Galbeta residues, which are particularly involved in the composition of the AB-glycotope.

20 citations

Journal ArticleDOI
TL;DR: The data suggest that the up-regulation of galectin-3 in the involuting mammary gland is not only controlled transcriptionally but also regulated posttranscriptionally under the control of systemic glucocorticoid hormones involved in coordinating the involution process.
Abstract: Galectin-3 is an endogenous mammalian lectin that binds to ABH carbohydrate antigens. Here we show that galectin-3 is strongly up-regulated during mammary gland involution and that it is expressed virtually exclusively on nonapoptotic cells. We demonstrate that dexamethasone, an inhibitor of the second phase of mammary gland involution, potently suppresses up-regulation of galectin-3 as judged immunohistochemically and on western blots, suggesting that systemic hormone levels regulate galectin-3 expression during involution. However, at the RNA level galectin-3 expression is rapidly up-regulated on the onset of involution but remains consistantly high during the first and second phase of involution regardless of dexamethasone treatment. These data suggest that the up-regulation of galectin-3 in the involuting mammary gland is not only controlled transcriptionally but also regulated posttranscriptionally under the control of systemic glucocorticoid hormones involved in coordinating the involution process.

20 citations


Cites background from "Expression of M-N#1, a histo-blood ..."

  • ...Note that the lactating mammary gland sample is overloaded to permit a glyceraldehyde-3-phosphate dehydrogenase (GAPDH) signal to be seen because we have previously shown that GAPDH expression is up-regulated during mammary gland involution (Mengwasser and Sleeman, 2001)....

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  • ...The essentially blood group B antigen M-N1 is strongly up-regulated in involuting mammary glands (Mengwasser and Sleeman, 2001)....

    [...]

  • ...Additionally, dexamethasone treatment inhibits tissue remodeling but not apoptosis in involuting mammary glands (Lund et al., 1996; Li et al., 1997; Mengwasser and Sleeman, 2001; data presented herein) and also suppresses galectin-3 expression (Figure 3, Figure 5, Table II)....

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  • ...We have previously demonstrated that the M-N1 antigen is not expressed on apoptosing cells in this context (Mengwasser and Sleeman, 2001)....

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  • ...Glucocorticoid hormones have been reported to be able to inhibit the second stage of involution in postlactating animals (Lund et al., 1996; Li et al., 1997; Mengwasser and Sleeman, 2001)....

    [...]

Journal ArticleDOI
TL;DR: Novel evidence for altered expression of proliferative antigens and enhanced expression of HBGA B in fibroblasts treated with dental monomers bis-GA and bis-GMA is presented suggesting that these substances affect cell morphology, proliferative activity, and antigenic profile.
Abstract: The present work is focused on examining the effect of the structurally similar dental monomers bis-GA and bis-GMA on the expression of histo-blood group antigens (HBGAs) in comparison with fibroblast vitality and proliferation. The fibroblast cell line McCoy-Plovdiv was cultivated in a serum-free medium and was treated with both monomers. Cell vitality was measured by the crystal violet test. Mitotic index and cell morphology were assessed. An immunocytochemical technique was applied to follow the expression of proliferative antigens PCNA and Ki-67 and of HBGA. The expression level of HBGA was measured by an improved pixel selection algorithm with proprietary software. The lowest concentration of 2.5 μmol/L did not significantly affect morphology, vitality, or proliferation activity. Interestingly, the quantitative analysis revealed augmented expression of HBGA B at 2.5 μmol/L. The higher concentrations of the dental monomers reduced cell vitality and mitotic indices and altered proliferative antigen expression. Bis-GA proved to be more toxic than bis-GMA and caused more prominent alterations including greater enhancement of HBGA B expression. We present novel evidence for altered expression of proliferative antigens and enhanced expression of HBGA B in fibroblasts treated with dental monomers bis-GA and bis-GMA suggesting that these substances affect cell morphology, proliferative activity, and antigenic profile.

3 citations


Cites background from "Expression of M-N#1, a histo-blood ..."

  • ...It was shown that a histo-blood group B-like antigen is strongly upregulated during rat mammary gland involution, implying that this antigen might either provide a survival function and/ or be expressed in epithelial cells destined to remodel mammary ducts (Mengwasser and Sleeman 2001)....

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References
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Journal ArticleDOI
TL;DR: Signaltransduction events such as activation of protein kinaseA and JNK3 and changes in the activity ofseveral transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1 during the early and late phases of mammary glandinvolution are described.
Abstract: Maintenance of mammary epithelial differentiation and milk production during lactation is a consequence of milk removal and the presence of lactogenic hormones, particularly glucocorticoids, insulin and prolactin. After weaning the fall in lactogenic hormones and milk stasis lead to involution, a process that is mainly characterized by three events: (i) downregulation of milk protein gene expression, (ii) loss of epithelial cells by apoptosis and, (iii) tissue remodeling and preparation of the gland for a new pregnancy. Each of these processes is likely to depend on the activity of specific sets of transcription factors in the mammary epithelium and stroma that ensure the timely and spatially coordinated expression of critical gene products such as mediators of apoptosis (e.g., caspase-1 and regulators of tissue remodeling events (e.g., matrix metalloproteinases). Here we describe signal transduction events such as activation of protein kinase A and JNK and changes in the activity of several transcription factors including Stat5, Stat3, NF1, Oct-1, and AP-1 during the early and late phases of mammary gland involution. We discuss their possible role in regulating and coordinating involution with emphasis on the apoptotic process of involution.

64 citations

Journal Article
TL;DR: In baboons ABH antigens are found on vascular endothelium but not on red blood cells, and this newly observed pattern of distribution is intermediate between that of lower mammals and that of humans, necessitating a reappraisal of current theory of the genetic control of tissue expression of ABHAntigens.

64 citations


"Expression of M-N#1, a histo-blood ..." refers background in this paper

  • ...Only humans and certain primates carry ABH antigens on endothelial cells and on erythrocytes (Oriol et al., 1994)....

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Journal ArticleDOI
TL;DR: Comparisons of carbohydrate profiles between control and apoptotic colon carcinoma cells were performed by flow cytometry using a set of lectins and anti-carbohydrate antibodies and it could be shown that the loss of H antigen after induction of apoptosis correlated with a loss of the carrier glycoprotein.
Abstract: Comparisons of carbohydrate profiles between control and apoptotic colon carcinoma cells were performed by flow cytometry using a set of lectins and anti-carbohydrate antibodies. The six cell lines analyzed presented distinct carbohydrate profiles before induction of apoptosis. PHA-L and MAA binding decreased after induction of apoptosis by UV-treatment. In contrast an increase of PNA binding was observed after induction of apoptosis, except on SW-48 cells for which a decrease occurred. A decrease of SNA binding was observed after induction of apoptosis from strongly positive control cell lines, whereas it increased on weakly positive ones. All the blood group related antigens A, H, Lewis a, Lewis x, Lewis b, and Lewis y, had their expression strongly diminished on apoptotic cells. These changes occurred irrespective of the mode of apoptosis induction since similar results were obtained after UV, TNFalpha, or anti-Fas treatment. Fucosyltransferases activities were also decreased after apoptosis induction, except for alpha1,3fucosyltransferase in anti-Fas treated HT-29 cells, where it was strongly augmented. This could be attributed to the IFNgamma preteatment required to induce Fas expression on these cells. Fucosidase activity decreased after induction of apoptosis suggesting that it was not responsible for the loss of fucosylated structures. In the rat PRO cell line, H blood group antigens are mainly carried by a high molecular weight variant of CD44. It could be shown that the loss of H antigen after induction of apoptosis correlated with a loss of the carrier glycoprotein.

54 citations

Journal ArticleDOI
TL;DR: The distribution, structures and probable biological functions of some of the blood group antigens in normal and pathological conditions are described.

44 citations

Book
01 Jan 1985
TL;DR: When you read more every page of this control of cell growth and proliferation, what you will obtain is something great.
Abstract: Read more and get great! That's what the book enPDFd control of cell growth and proliferation will give for every reader to read this book. This is an on-line book provided in this website. Even this book becomes a choice of someone to read, many in the world also loves it so much. As what we talk, when you read more every page of this control of cell growth and proliferation, what you will obtain is something great.

41 citations