Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1996-7-10
pubmed:abstractText
CRIPTO is a member of the epidermal growth factor (EGF) gene family originally isolated from undifferentiated human NTERA2 clone D1 (NT2D1) multipotent embryonal carcinoma cells. Retinoic acid (RA) treatment of NT2D1 cells leads to a neuronal differentiation program and to concomitant loss of CRIPTO mRNA expression. To assess the role of CRIPTO in the control of NT2D1 cell growth or differentiation, these cells were treated with 3 anti-sense oligodeoxynucleotides complementary to the 5' end of the human CRIPTO mRNA. A dose-dependent inhibition of monolayer and soft agar growth was observed with each of these CRIPTO anti-sense oligodeoxynucleotides but not with a control oligodeoxynucleotide of random sequence or with the 3 corresponding CRIPTO sense oligodeoxynucleotides. In addition, NT2D1 cells were transfected with a recombinant expression vector containing a 918-bp coding fragment of the human CRIPTO cDNA in the 3' to 5' orientation. NT2D1 CRIPTO anti-sense transfectants exhibited a significantly reduced endogenous CRIPTO mRNA and protein, a 4- to 5-fold decrease in growth rate in monolayer and a 50-70% reduction in cloning efficiency in soft agar as compared with NT2D1 parental cells or with NT2D1 cells transfected with a plasmid containing the neomycin-resistance gene alone (NT2D1 neo cells). Finally, we examined the expression of immunophenotypic markers that are modulated during the differentiation of NT2D1 cells following RA treatment. The globoseries stage-specific embryonic antigen-3 recognized by the monoclonal antibody (MAb) SSEA-3 was expressed in 60% of undifferentiated parental NT2D1 or NT2D1 neo cells and in only 20% of NT2D1 CRIPTO anti-sense transfectants, whereas it was down-regulated in all cell lines following RA treatment. A neuroectodermal antigen recognized by the A2B5 MAb, which was not expressed in parental NT2D1, in NT2D1 neo or in CRIPTO anti-sense NT2D1 cells, was induced by RA treatment in all cell lines. Taken together, our results show that inhibition of endogenous CRIPTO expression in human embryonal carcinoma cells interferes with both transformation and differentiation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
16
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
538-43
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:8635871-Base Sequence, pubmed-meshheading:8635871-Carcinoma, Embryonal, pubmed-meshheading:8635871-Cell Adhesion, pubmed-meshheading:8635871-Cell Differentiation, pubmed-meshheading:8635871-Cell Division, pubmed-meshheading:8635871-Cell Transformation, Neoplastic, pubmed-meshheading:8635871-DNA Primers, pubmed-meshheading:8635871-Epidermal Growth Factor, pubmed-meshheading:8635871-GPI-Linked Proteins, pubmed-meshheading:8635871-Growth Substances, pubmed-meshheading:8635871-Humans, pubmed-meshheading:8635871-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:8635871-Membrane Glycoproteins, pubmed-meshheading:8635871-Molecular Sequence Data, pubmed-meshheading:8635871-Neoplasm Proteins, pubmed-meshheading:8635871-Plasmids, pubmed-meshheading:8635871-RNA, Antisense, pubmed-meshheading:8635871-Transfection, pubmed-meshheading:8635871-Tumor Cells, Cultured
pubmed:year
1996
pubmed:articleTitle
Transfection with a CRIPTO anti-sense plasmid suppresses endogenous CRIPTO expression and inhibits transformation in a human embryonal carcinoma cell line.
pubmed:affiliation
Cattedra di Oncologia Medica, Università degli Studi di Napoli Federico II, Naples, Italy.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't