• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of molcellbPermissionsJournals.ASM.orgJournalMCB ArticleJournal InfoAuthorsReviewers
Mol Cell Biol. Nov 1991; 11(11): 5446–5453.
PMCID: PMC361913

Expression of CD44 is repressed in neuroblastoma cells.


We have used cDNA subtractive cloning to identify a group of human genes that are expressed in diverse differentiated derivatives of neural crest origin but not in neuroblastoma cell lines. One of these genes was identified as CD44, which encodes an integral membrane glycoprotein that serves as the principal receptor for hyaluronate and participates in specific cell-cell and cell-extracellular matrix interactions. The repression of CD44 expression in neuroblastoma cell lines might be relevant to their high metastatic potential. We have cloned full-length cDNAs corresponding to CD44 trancscripts and identified a novel splice variant of CD44 lacking 31 amino acids of the extracellular domain. As a first step toward analysis of CD44 downregulation in neuroblastoma cells, we have mapped the CD44 RNA initiation site and analyzed the structure of the upstream regulatory region. We constructed a series of plasmids containing different amounts of CD44 upstream regulatory region linked to the bacterial chloramphenicol acetyltransferase gene and then analyzed their ability to promote transcription in neuroblastoma and melanoma cells. We found that a DNA segment including about 150 bp of the CD44 upstream region and the 5' end of the gene itself was sufficient to induce substantial transcription of the chloramphenicol acetyltransferase gene in both neuroblastoma and melanoma cells. Several upstream cis-acting elements contribute to the downregulation of CD44 in neuroblastoma cells, the most prominent being a 120-bp DNA fragment located 450 bp upstream to the RNA initiation site. Our data suggest that multiple factors might be involved in downregulation of CD44 in neuroblastoma cells.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.5M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Akeson R, Bernards R. N-myc down regulates neural cell adhesion molecule expression in rat neuroblastoma. Mol Cell Biol. 1990 May;10(5):2012–2016. [PMC free article] [PubMed]
  • Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. [PubMed]
  • Belitsos PC, Hildreth JE, August JT. Homotypic cell aggregation induced by anti-CD44(Pgp-1) monoclonal antibodies and related to CD44(Pgp-1) expression. J Immunol. 1990 Mar 1;144(5):1661–1670. [PubMed]
  • Bernards R, Dessain SK, Weinberg RA. N-myc amplification causes down-modulation of MHC class I antigen expression in neuroblastoma. Cell. 1986 Dec 5;47(5):667–674. [PubMed]
  • Bishop JM. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. [PubMed]
  • Brodeur GM, Sekhon G, Goldstein MN. Chromosomal aberrations in human neuroblastomas. Cancer. 1977 Nov;40(5):2256–2263. [PubMed]
  • Carter WG, Wayner EA. Characterization of the class III collagen receptor, a phosphorylated, transmembrane glycoprotein expressed in nucleated human cells. J Biol Chem. 1988 Mar 25;263(9):4193–4201. [PubMed]
  • Cooper MJ, Hutchins GM, Cohen PS, Helman LJ, Mennie RJ, Israel MA. Human neuroblastoma tumor cell lines correspond to the arrested differentiation of chromaffin adrenal medullary neuroblasts. Cell Growth Differ. 1990 Apr;1(4):149–159. [PubMed]
  • Culty M, Miyake K, Kincade PW, Sikorski E, Butcher EC, Underhill C, Silorski E. The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins. J Cell Biol. 1990 Dec;111(6 Pt 1):2765–2774. [PMC free article] [PubMed]
  • Gilbert F, Feder M, Balaban G, Brangman D, Lurie DK, Podolsky R, Rinaldt V, Vinikoor N, Weisband J. Human neuroblastomas and abnormalities of chromosomes 1 and 17. Cancer Res. 1984 Nov;44(11):5444–5449. [PubMed]
  • Goldstein LA, Butcher EC. Identification of mRNA that encodes an alternative form of H-CAM(CD44) in lymphoid and nonlymphoid tissues. Immunogenetics. 1990;32(6):389–397. [PubMed]
  • Goldstein LA, Zhou DF, Picker LJ, Minty CN, Bargatze RF, Ding JF, Butcher EC. A human lymphocyte homing receptor, the hermes antigen, is related to cartilage proteoglycan core and link proteins. Cell. 1989 Mar 24;56(6):1063–1072. [PubMed]
  • Günthert U, Hofmann M, Rudy W, Reber S, Zöller M, Haussmann I, Matzku S, Wenzel A, Ponta H, Herrlich P. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991 Apr 5;65(1):13–24. [PubMed]
  • Huet S, Groux H, Caillou B, Valentin H, Prieur AM, Bernard A. CD44 contributes to T cell activation. J Immunol. 1989 Aug 1;143(3):798–801. [PubMed]
  • Haynes BF, Telen MJ, Hale LP, Denning SM. CD44--a molecule involved in leukocyte adherence and T-cell activation. Immunol Today. 1989 Dec;10(12):423–428. [PubMed]
  • Hedrick SM, Cohen DI, Nielsen EA, Davis MM. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. [PubMed]
  • Idzerda RL, Carter WG, Nottenburg C, Wayner EA, Gallatin WM, St John T. Isolation and DNA sequence of a cDNA clone encoding a lymphocyte adhesion receptor for high endothelium. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4659–4663. [PMC free article] [PubMed]
  • Jalkanen S, Reichert RA, Gallatin WM, Bargatze RF, Weissman IL, Butcher EC. Homing receptors and the control of lymphocyte migration. Immunol Rev. 1986 Jun;91:39–60. [PubMed]
  • Lewinsohn DM, Nagler A, Ginzton N, Greenberg P, Butcher EC. Hematopoietic progenitor cell expression of the H-CAM (CD44) homing-associated adhesion molecule. Blood. 1990 Feb 1;75(3):589–595. [PubMed]
  • Miyake K, Medina KL, Hayashi S, Ono S, Hamaoka T, Kincade PW. Monoclonal antibodies to Pgp-1/CD44 block lympho-hemopoiesis in long-term bone marrow cultures. J Exp Med. 1990 Feb 1;171(2):477–488. [PMC free article] [PubMed]
  • Miyake K, Underhill CB, Lesley J, Kincade PW. Hyaluronate can function as a cell adhesion molecule and CD44 participates in hyaluronate recognition. J Exp Med. 1990 Jul 1;172(1):69–75. [PMC free article] [PubMed]
  • Picker LJ, Nakache M, Butcher EC. Monoclonal antibodies to human lymphocyte homing receptors define a novel class of adhesion molecules on diverse cell types. J Cell Biol. 1989 Aug;109(2):927–937. [PMC free article] [PubMed]
  • Sehgal A, Patil N, Chao M. A constitutive promoter directs expression of the nerve growth factor receptor gene. Mol Cell Biol. 1988 Aug;8(8):3160–3167. [PMC free article] [PubMed]
  • Shimizu Y, Van Seventer GA, Siraganian R, Wahl L, Shaw S. Dual role of the CD44 molecule in T cell adhesion and activation. J Immunol. 1989 Oct 15;143(8):2457–2463. [PubMed]
  • Sidell N, Altman A, Haussler MR, Seeger RC. Effects of retinoic acid (RA) on the growth and phenotypic expression of several human neuroblastoma cell lines. Exp Cell Res. 1983 Oct;148(1):21–30. [PubMed]
  • Smale ST, Baltimore D. The "initiator" as a transcription control element. Cell. 1989 Apr 7;57(1):103–113. [PubMed]
  • Sonnenfeld KH, Ishii DN. Nerve growth factor effects and receptors in cultured human neuroblastoma cell lines. J Neurosci Res. 1982;8(2-3):375–391. [PubMed]
  • Spinelli W, Sonnenfeld KH, Ishii DN. Effects of phorbol ester tumor promoters and nerve growth factor on neurite outgrowth in cultured human neuroblastoma cells. Cancer Res. 1982 Dec;42(12):5067–5073. [PubMed]
  • Stamenkovic I, Amiot M, Pesando JM, Seed B. A lymphocyte molecule implicated in lymph node homing is a member of the cartilage link protein family. Cell. 1989 Mar 24;56(6):1057–1062. [PubMed]
  • Stamenkovic I, Aruffo A, Amiot M, Seed B. The hematopoietic and epithelial forms of CD44 are distinct polypeptides with different adhesion potentials for hyaluronate-bearing cells. EMBO J. 1991 Feb;10(2):343–348. [PMC free article] [PubMed]
  • St John T, Meyer J, Idzerda R, Gallatin WM. Expression of CD44 confers a new adhesive phenotype on transfected cells. Cell. 1990 Jan 12;60(1):45–52. [PubMed]
  • Thiery JP, Duband JL, Rutishauser U, Edelman GM. Cell adhesion molecules in early chicken embryogenesis. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6737–6741. [PMC free article] [PubMed]
  • Tsokos M, Scarpa S, Ross RA, Triche TJ. Differentiation of human neuroblastoma recapitulates neural crest development. Study of morphology, neurotransmitter enzymes, and extracellular matrix proteins. Am J Pathol. 1987 Sep;128(3):484–496. [PMC free article] [PubMed]
  • Weith A, Martinsson T, Cziepluch C, Brüderlein S, Amler LC, Berthold F, Schwab M. Neuroblastoma consensus deletion maps to 1p36.1-2. Genes Chromosomes Cancer. 1989 Nov;1(2):159–166. [PubMed]
  • Whang-Peng J, Triche TJ, Knutsen T, Miser J, Kao-Shan S, Tsai S, Israel MA. Cytogenetic characterization of selected small round cell tumors of childhood. Cancer Genet Cytogenet. 1986 Apr 1;21(3):185–208. [PubMed]
  • Zhou DF, Ding JF, Picker LJ, Bargatze RF, Butcher EC, Goeddel DV. Molecular cloning and expression of Pgp-1. The mouse homolog of the human H-CAM (Hermes) lymphocyte homing receptor. J Immunol. 1989 Nov 15;143(10):3390–3395. [PubMed]

Articles from Molecular and Cellular Biology are provided here courtesy of American Society for Microbiology (ASM)


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Gene
    Gene links
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence links
  • GEO Profiles
    GEO Profiles
    Related GEO records
  • HomoloGene
    HomoloGene links
  • MedGen
    Related information in MedGen
  • Nucleotide
    Published Nucleotide sequences
  • OMIM
    OMIM record citing PubMed
  • Pathways + GO
    Pathways + GO
    Pathways, annotations and biological systems (BioSystems) that cite the current article.
  • Protein
    Published protein sequences
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...