Glycoconjugate Journal

, Volume 19, Issue 7–9, pp 441–449 | Cite as

Galectin genes: Regulation of expression

  • Lorenzo Chiariotti
  • Paola Salvatore
  • Rodolfo Frunzio
  • Carmelo B. Bruni


In this review we have summarized the more recent studies on the expression of mammalian galectins. One interesting observation that can be made is that in most of microarrays and/or differential display analysis performed in recent years one or more galectins have been picked up. From a critical evaluation of the pertinent studies the main conclusion that can be drawn is that, although it is not yet clear whether the 14 galectins identified so far have functions in common, a striking common feature of all galectins is the strong modulation of their expression during development, differentiation stages and under different physiological or pathological conditions. This suggests that the expression of different galectins is finely tuned and possibly coordinated. In spite of these observations it is rather unexpected that very few studies have been performed on the molecular mechanisms governing the activity of galectin genes. Published in 2004.

galectins transcriptional regulation gene expression 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Barondes SH and 20 others, Galectins: A family of animal β-galactoside-binding lectins, Cell 76, 597-8 (1994).Google Scholar
  2. 2.
    Leffler H, Introduction to galectins, Trends Glycosci Glycotech 9, 9-19 (1997).Google Scholar
  3. 3.
    Cooper DNW, Barondes SH, God must love galectins; he made so many of them, Glycobiology 9, 979-84 (1999).Google Scholar
  4. 4.
    Rabinovich GA, Baum LG, Tinari N, Paganelli R, Natoli C, Liu FT, Iacobelli S, Galectins and their ligands: Amplifiers, silencers or tuners of the inflammatory response?, Trends Immunol 23, 313-20 (2002).Google Scholar
  5. 5.
    Barondes SH, Cooper DNW, Gitt MA, Leffler H, Structure and function of a large family of animal lectins, J Biol Chem 269, 20807-10 (1994).Google Scholar
  6. 6.
    Leffler H, Galectins structure and function-a synopsis, Results Probl Cell Differ 33, 57-83 (2001).Google Scholar
  7. 7.
    Bidon N, Brichory F, Bourguet P, Le Pennec JP, Dazord L, Galectin-8: A complex sub-family of galectins, Int J Mol Med 8, 245-50 (2001).Google Scholar
  8. 8.
    Hughes RC, Galectins as modulators of cell adhesion, Biochimie 83, 667-76 (2001).Google Scholar
  9. 9.
    Akahani S, Inohara H, Nangia-Makker P, Raz A, Galectin-3 in tumor metastasis, Trends Glycosci Glycotech 9, 69-75 (1997).Google Scholar
  10. 10.
    Chiariotti L, Salvatore P, Benvenuto G, Bruni CB, Control of galectin gene expression, Biochimie 81, 381-8 (1999).Google Scholar
  11. 11.
    Paz A, Haklai R, Elad-Sfadia G, Ballan E, Kloog Y, Galectin-1 binds oncogenic H-Ras to mediate Ras membrane anchorage and cell transformation, Oncogene 20, 7486-93 (2001).Google Scholar
  12. 12.
    Elad-Sfadia G, Haklai R, Ballan E, Gabius HJ, Kloog Y, Galectin-1 augments ras activation and diverts ras signals to Raf-1 at the expense of phosphoinositide 3-kinase, J Biol Chem, in Press (2002).Google Scholar
  13. 13.
    Van den Brule FA, Castronovo V, Laminin-binding lectins during invasion and metastasis. In Lectins and Pathology, edited by Caron M, Seve AP (Harwood Academic Publishers, 1999), pp. 79-121.Google Scholar
  14. 14.
    Nangia-Makker P, Conklin J, Hogan V, Raz A, Carbohydrate-binding proteins in cancer, and their ligands as therapeutic agents, Trends Mol Med 8, 187-92 (2002).Google Scholar
  15. 15.
    Perillo NL, Pace KE, Seilhamer JJ, Baum LG, Apoptosis of T cells mediated by galectin-1, Nature 378, 736-9 (1995).Google Scholar
  16. 16.
    Akahani S, Nangia-Makker P, Inohara H, Choi Kim HR, Raz A, Galectin-3: A novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family, Cancer Res 57, 5272-6 (1997).Google Scholar
  17. 17.
    Pace KE, Baum LG, Induction of T lymphocyte apoptosis:Anovel function for galectin-1 Trends Glycosci Glycotech 9, 21-9 (1997).Google Scholar
  18. 18.
    Bernerd F, Sarasin A, Magnaldo T, Galectin-7 overexpression is associated with the apoptotic process in UVB-induced sunburn keratinocytes, Proc Natl Acad Sci USA 96, 11329-34 (1999).. Google Scholar
  19. 19.
    Pace KE, Lee C, Stewart PL, Baum LG, Restricted receptor segregation into membrane microdomains occurs on human T cells during apoptosis induced by galectin-1, J Immunol 163, 3801-11 (1999).Google Scholar
  20. 20.
    Chung CD, Patel VP, Moran M, Lewis LA, Carrie Miceli M, Galectin-1 induces partial TCR zeta-chain phosphorylation and antagonizes processive TCR signal transduction, J Immunol 165, 3722-9 (2000).Google Scholar
  21. 21.
    Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y, Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis, J Cell Sci 113, 2385-97 (2000).Google Scholar
  22. 22.
    Pace KE, Hahn HP, Pang M, Nguyen JT, Baum LG, CD7 delivers a pro-apoptotic signal during galectin-1-induced T cell death, J Immunol 165, 2331-4 (2000).Google Scholar
  23. 23.
    Rabinovich GA, Alonso CR, Sotomayor CE, Durand S, Bocco JL, Riera CM, Molecular mechanisms implicated in galectin-1-induced apoptosis: Activation of the AP-1 transcription factor and downregulation of Bcl-2, Cell Death Differ 7, 747-53 (2000).Google Scholar
  24. 24.
    Hotta K, Funahashi T, Matsukawa Y, Takahashi M, Nishizawa H, Kishida K, Matsuda M, Kuriyama H, Kihara S, Nakamura T, Tochino Y, Bodkin NL, Hansen BC, Matsuzawa Y, Galectin-12, an adipose-expressed galectin-like molecule possessing apoptosisinducing activity, J Biol Chem 276, 34089-97 (2001).Google Scholar
  25. 25.
    Kuwabara I, Kuwabara Y, Yang RY, Schuler M, Green DR, Zuraw BL, Hsu DK, Liu FT, Galectin-7 (PIG1) exhibits pro-apoptotic function through JNK activation and mitochondrial cytochrome c release, J Biol Chem 277, 3487-97 (2002).Google Scholar
  26. 26.
    Matsumoto R, Matsumoto H, Seki M, Hata M, Asano Y, Kanegasaki S, Stevens RL, Hirashima M, Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes, J Biol Chem 273, 16976-84 (1998).Google Scholar
  27. 27.
    Liu FT, Galectins: A new family of regulators of inflammation, Clin Immunol 97, 79-88 (2000).Google Scholar
  28. 28.
    Dunphy JL, Barcham GJ, Bischof RJ, Young AR, Nash A, Meeusen EN, Isolation and characterization of a novel eosinophilspecific galectin released into the lungs in response to allergen challenge, J Biol Chem 277, 14916-24 (2002).Google Scholar
  29. 29.
    Colnot C, Ripoche MA, Fowlis D, Cannon V, Scaerou F, Cooper D, Poirier F, The role of galectins in mouse development, Trends Glycosci Glycotech 9, 31-40 (1997).Google Scholar
  30. 30.
    Puche AC, Poirier F, Hair M, Bartlett PF, Key B, Role of galectin-1 in the developing mouse olfactory system, Dev Biol 179, 274-87 (1996).Google Scholar
  31. 31.
    Key B, Puche AC, Role of galectin-1 in the olfactory nervous system, Trends Glycosci Glycotech 9, 41-5 (1997).Google Scholar
  32. 32.
    Goldring K, Jones GE, Thiagarajah R, Watt DJ, The effect of galectin-1 on the differentiation of fibroblasts and myoblasts in vitro, J Cell Sci 115, 355-66 (2002).Google Scholar
  33. 33.
    Magnaldo T, Darmon M, Galectin-7, a new marker of mammalian stratified epithelia, Trends Glycosci Glycotech 9, 95-102 (1997).Google Scholar
  34. 34.
    Magnaldo T, Fowlis D, Darmon M, Galectin-7, a marker of all types of stratified epithelia, Differentiation 3, 159-68 (1998).Google Scholar
  35. 35.
    Colnot C, Fowlis D, Ripoche MA, Bouchaert I, Poirier F, Embryonic implantation in galectin 1/galectin 3 double mutant mice, Dev Dyn 211, 306-13 (1998).Google Scholar
  36. 36.
    Dagher SF, Wang JL, Patterson RL, (1995) Identification of galectin-3 as a factor in pre-mRNA splicing, Proc Natl Acad Sci USA 92, 1213-17 (1997).Google Scholar
  37. 37.
    Vyakarnam A, Dagher SF, Wang JL, Patterson RJ, Evidence for a role for galectin-1 in pre-mRNA splicing, Mol Cell Biol 17, 4730- 37 (1997).Google Scholar
  38. 38.
    Lipkowitz MS, Leal-Pinto E, Rappoport JZ, Najfeld V, Abramson RG, Functional reconstitution, membrane targeting, genomic structure, and chromosomal localization of a human urate transporter, J Clin Invest 107, 1103-15 (2001).Google Scholar
  39. 39.
    Spitzenberger F, Graessler J, Schroeder HE, Molecular and functional characterization of galectin 9 mRNA isoforms in porcine and human cells and tissues, Biochimie 83, 851-62 (2001).Google Scholar
  40. 40.
    Dyer KD, Rosenberg HF, Eosinophil Charcot-Leyden crystal protein binds to beta-galactoside sugars, Life Sci 58, 2073-82 (1996).Google Scholar
  41. 41.
    Gitt MA, Jordan ET, Leffler H, galectin-2, Galectins-5 and-9, and galectins-4 and-6, Trends Glycosci Glycotech 9, 87-93 (1997).Google Scholar
  42. 42.
    Wada J, Ota K, Kumar A, Wallner EI, Kanwar YS, Developmental regulation, expression, and apoptotic potential of galectin-9, a β-galactoside binding lectin, J Clin Invest 99, 2452-61 (1997).Google Scholar
  43. 43.
    Ogden AT, Nunes I, Ko K, Wu S, Hines CS, Wang AF, Hegde RS, Lang RA, GRIFIN, a novel lens-specific protein related to the galectin family, J Biol Chem 273, 28889-96 (1998).Google Scholar
  44. 44.
    Chiariotti L, Berlingieri MT, De Rosa P, Battaglia C, Berger N, Bruni CB, Fusco A, Increased expression of the negative growth factor, galactoside-binding protein gene in transformed thyroid cells and in human thyroid carcinomas, Oncogene 7, 2507-11 (1992).Google Scholar
  45. 45.
    Chiariotti L, Berlingieri MT, Battaglia C, Benvenuto G, Martelli ML, Salvatore P, Chiappetta G, Bruni CB, Fusco A, Expression of galectin-1 in normal human thyroid gland and in differentiated and poorly differentiated thyroid tumors, Int J Cancer(Pred Oncol) 64, 171-5 (1995).Google Scholar
  46. 46.
    Xu XC, el-Naggar AK, Lotan R, Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications, Am J Pathol 147, 815-22 (1995).Google Scholar
  47. 47.
    Fernandez PL, Merino MJ, Gomez M, Campo E, Medina T, Castronovo V, Sanjuan X, Cardesa A, Galectin-3 and laminin expression in neoplastic and non-neoplastic thyroid tissue, J Pathol 181, 80-6 (1997).Google Scholar
  48. 48.
    Orlandi F, Saggiorato E, Pivano G, Puligheddu B, Termine A, Cappia S, De Giuli P, Angeli A, Galectin-3 is a pre-surgical marker of human thyroid carcinoma, Cancer Res 58, 3015-20 (1998).Google Scholar
  49. 49.
    Bartolazzi A, Gasbarri A, Papotti M, Bussolati G, Lucante T, Khan A, Inohara H, Marandino F, Orlandi F, Nardi F, Vecchione A, Tecce R, Larsson O, Application of an immunodiagnostic method for improving preoperative diagnosis of nodular thyroid lesions, Lancet 357, 1644-50 (2001).Google Scholar
  50. 50.
    Rechreche H, Mallo GV, Montalto G, Dagorn JC, Iovanna JL, Cloning and expression of the mRNA of human galectin-4, an Stype lectin down-regulated in colorectal cancer, Eur J Biochem 248, 225-30 (1997).Google Scholar
  51. 51.
    Sanjuàn X, Fernandez PL, Castells A, Castronovo V, van den Brûle F, Liu FT, Cardesa A, Campo E, Differential expression of galectin-3 and galectin-1 in colorectal cancer progression, Gastroenterology 113, 1906-15 (1997).Google Scholar
  52. 52.
    Gitt MA, Colnot C, Poirier F, Nani KJ, Barondes SH, Leffler H, Galectin-4 and galectin-6 are two closely related lectins expressed in mouse gastrointestinal tract, J Biol Chem 273, 2954-60 (1998).Google Scholar
  53. 53.
    Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van Ham P, Yeaton P, Pector JC, Zick Y, Salmon I, Danguy A, Kiss R, Gabius HJ, Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor, Gut 50, 392-401 (2002).Google Scholar
  54. 54.
    Pienta JK, Naik H, Akhtar A, Yamazaki K, Replogle TS, Lehr J, Donat TT, Tait L, Hogan V, Raz A, Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin, J Natl Cancer Inst 87, 348-53 (1995).Google Scholar
  55. 55.
    Chiariotti L, Benvenuto G, Salvatore P, Veneziani BM, Villone G, Fusco A, Russo T, Bruni CB, Expression of the soluble lectin L-14 gene is induced by TSH in thyroid cells and suppressed by retinoic acid in transformed neural cells, Biochem Biophys Res Commun 199, 540-6 (1994).Google Scholar
  56. 56.
    Gillenwater A, Xu XC, Estrov Y, Sacks PG, Lotan D, Lotan R, Modulation of galectin-1 content in human head and neck squamous carcinoma cells by sodium butyrate, Int J Cancer 75, 217-24 (1998).Google Scholar
  57. 57.
    Baum LG, Seilhamer JJ, Pang M, Levine WB, Beynon D, Berliner JA, Synthesis of an endogenous lectin, galectin-1, by human endothelial cells is up-regulated by endothelial cell activation, Glycoconj J 12, 63-8 (1995).Google Scholar
  58. 58.
    Chiariotti L, Benvenuto G, Zarrilli R, Rossi E, Salvatore P, Colantuoni V, Bruni CB, Activation of the galectin-1 (L-14-I) gene from non-expressing differentiated cells by fusion with undifferentiated and tumorigenic cells, Cell Growth &; Differ 5, 769-75 (1994).Google Scholar
  59. 59.
    Salvatore P, Benvenuto G, Pero R, Lembo F, Bruni CB, Chiariotti L, Galectin-1 gene expression and methylation state in human T leukemia cell lines, Int J Oncol 17, 1015-8 (2000).Google Scholar
  60. 60.
    Poirier F, Bourin P, Bladier D, Joubert-Caron R, Caron M, Effect of 5-azacytidine and galectin-1 on growth and differentiation of the human b lymphoma cell line bl36, Cancer Cell Int 1, 2 (2001).Google Scholar
  61. 61.
    Lu Y, Amos B, Cruise E, Lotan D, Lotan R, A parallel association between differentiation and induction of galectin-1, and inhibition of galectin-3 by retinoic acid in mouse embryonal carcinoma F9 cells, Biol Chem 379, 1323-31 (1998).Google Scholar
  62. 62.
    Hsu DK, Hammes SR, Kuwabara I, Greene WC, Liu F-T, Human T lymphotropic virus-I infection of human T lymphocytes induces expression of the β-galactoside-binding lectin, galectin-3, Am J Pathol 148, 1661-70 (1996).Google Scholar
  63. 63.
    Fogel S, Guittaut M, Legrand A, Monsigny M, Hebert E, The tat protein of HIV-1 induces galectin-3 expression, Glycobiology 9, 383-7 (1999).Google Scholar
  64. 64.
    Magnaldo T, Bernerd F, Darmon M, Galectin-7, a human 14-kDa S-lectin, specifically expressed in keratinocytes and sensitive to retinoic acid, Developmental Biol 168, 259-71 (1995).Google Scholar
  65. 65.
    Gitt MA, Massa SM, Leffler H, Barondes SH, Isolation and expression of a gene encoding L-14-II, a new human soluble lactosebinding lectin, J Biol Chem 267, 10601-06 (1992).Google Scholar
  66. 66.
    Gomolin H, Yamaguchi Y, Paulpillai AV, Dvorak LA, Ackerman SJ, Tenen DG, Human eosinophil Charcot-Leyden Crystal Protein: Cloning and characterization of a lysophospholipase gene promoter, Blood 82, 1868-74 (1993).Google Scholar
  67. 67.
    Raimond J, Rouleux F, Monsigny M, Legrand A, The second intron of the human galectin-3 gene has a strong promoter activity down-regulated by p-53, FEBS Lett 363, 165-9 (1995).Google Scholar
  68. 68.
    Salvatore P, Contursi C, Benvenuto G, Bruni CB, Chiariotti L, Characterization and functional dissection of the galectin-1 gene promoter, FEBS Lett 373, 159-63 (1995).Google Scholar
  69. 69.
    Kadrofske MM, Kyle PO, Wang JL, The human LGALS3 (galectin-3) gene: Determination of the gene structure and functional characterization of the promoter, Arch Bioch Biophys 349, 7-20 (1998).Google Scholar
  70. 70.
    Lu Y, Lotan D, Lotan R, Differential regulation of constitutive and retinoic acid-induced galectin-1 gene transcription in murine embryonal carcinoma and myoblastic cells, Biochim Biophys Acta 1491, 13-9 (2000).Google Scholar
  71. 71.
    De Gregorio E, Chiariotti L, Di Nocera PP, The overlap of Inr and TATA elements sets the use of alternative transcriptional start sites in the mouse galectin-1 gene promoter, Gene 268, 215-23 (2001).Google Scholar
  72. 72.
    Lu Y, Lotan R, Transcriptional regulation by butyrate of mouse galectin-1 gene in embryonal carcinoma cells, Biochim Biophys Acta 1444, 85-91 (1999).Google Scholar
  73. 73.
    Lutterbach B, Hiebert SW, Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation, Gene 245, 223-35 (2000).Google Scholar
  74. 74.
    Guittaut M, Charpentier S, Normand T, Dubois M, Raimond J, Legrand A, Identification of an internal gene to the human Galectin-3 gene with two different overlapping reading frames that do not encode galectin-3, J Biol Chem 276, 2652-7 (2001).Google Scholar
  75. 75.
    Gaudin JC, Arar C, Monsigny M, Legrand A, Modulation of the expression of the rabbit galectin-3 gene by p53 and c-Ha-ras proteins and PMA, Glycobiology 7, 1089-98 (1997).Google Scholar
  76. 76.
    Gitt MA, Xia YR, Atchison RE, Lusis AJ, Barondes SH, Leffler H, Sequence, structure, and chromosomal mapping of the mouse Lgals6 gene, encoding galectin-6, J Biol Chem 273, 2961-70 (1998).Google Scholar
  77. 77.
    Dyer KD, Rosenberg HF, Transcriptional regulation of galectin-10 (eosinophil Charcot-Leyden crystal protein): A GC box (–44 to–50) controls butyric acid induction of gene expression, Life Sci 69, 201-12 (2001).Google Scholar
  78. 78.
    Jones PA, Laird PW, Cancer epigenetics comes of age, Nat Genet 21, 163-7 (1999).Google Scholar
  79. 79.
    Baylin SB, Herman JG, DNA hypermethylation in tumorigenesis: Epigenetics joins genetics, Trends Genet 16, 168-74 (2000).Google Scholar
  80. 80.
    Cindolo L, Benvenuto G, Salvatore P, Pero R, Salvatore G, Mirone V, Prezioso D, Altieri V, Bruni CB, Chiariotti L, Galectin-1 and galectin-3 expression in human bladder transitional-cell carcinomas, Int J Cancer 84, 39-43 (1999).Google Scholar
  81. 81.
    Benvenuto G, Carpentieri ML, Salvatore P, Cindolo L, Bruni CB, Chiariotti L, Cell-specific transcriptional regulation and reactivation of galectin-1 gene expression are controlled by DNA methylation of the promoter region, Mol Cell Biol 16, 2736-43 (1996).Google Scholar
  82. 82.
    Salvatore P, Benvenuto G, Caporaso M, Bruni CB, Chiariotti L, High resolution methylation analysis of the galectin-1 gene promoter region in expressing and nonexpressing tissues, FEBS Lett 421, 152-8 (1998).Google Scholar

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • Lorenzo Chiariotti
    • 1
  • Paola Salvatore
    • 2
  • Rodolfo Frunzio
    • 3
  • Carmelo B. Bruni
    • 2
  1. 1.Dipartimento di Medicina Sperimentale e ClinicaUniversità degli Studi “Magna Graecia” di CatanzaroCatanzaro
  2. 2.Dipartimento di Biologia e Patologia Cellulare e Molecolare “L. Califano”Università degli Studi di Napoli “Federico II”, Istituto di Endocrinologia ed Oncologia Sperimentale “G. Salvatore” of the Consiglio Nazionale delle RicercheItaly
  3. 3.Dipartimento di Chimica BiologicaUniversità degli Studi di Napoli “Federico II”NapoliItaly

Personalised recommendations