Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors
Identifieur interne : 002F78 ( Main/Exploration ); précédent : 002F77; suivant : 002F79Cripto: Expression, epigenetic regulation and potential diagnostic use in testicular germ cell tumors
Auteurs : Cassy M. Spiller ; Ad J. M. Gillis ; Guillaume Burnet ; Hans Stoop ; Peter Koopman ; Josephine Bowles ; Leendert H. J. LooijengaSource :
- Molecular Oncology [ 1574-7891 ] ; 2015.
Descripteurs français
- KwdFr :
- Animaux, Carcinome embryonnaire (diagnostic), Carcinome embryonnaire (génétique), Carcinome embryonnaire (sang), Facteur de croissance épidermique (biosynthèse), Facteur de croissance épidermique (génétique), Glycoprotéines membranaires (biosynthèse), Glycoprotéines membranaires (génétique), Humains, Mâle, Protéines et peptides de signalisation intercellulaire (biosynthèse), Protéines et peptides de signalisation intercellulaire (génétique), Protéines liées au GPI (biosynthèse), Protéines liées au GPI (génétique), Protéines tumorales (biosynthèse), Protéines tumorales (génétique), Régulation de l'expression des gènes tumoraux, Souris, Souris transgéniques, Tumeurs du testicule (diagnostic), Tumeurs du testicule (génétique), Tumeurs du testicule (sang), Épigenèse génétique.
- MESH :
- biosynthèse : Facteur de croissance épidermique, Glycoprotéines membranaires, Protéines et peptides de signalisation intercellulaire, Protéines liées au GPI, Protéines tumorales.
- diagnostic : Carcinome embryonnaire, Tumeurs du testicule.
- génétique : Carcinome embryonnaire, Facteur de croissance épidermique, Glycoprotéines membranaires, Protéines et peptides de signalisation intercellulaire, Protéines liées au GPI, Protéines tumorales, Tumeurs du testicule.
- sang : Carcinome embryonnaire, Tumeurs du testicule.
- Animaux, Humains, Mâle, Régulation de l'expression des gènes tumoraux, Souris, Souris transgéniques, Épigenèse génétique.
English descriptors
- KwdEn :
- Animals, Carcinoma, Embryonal (blood), Carcinoma, Embryonal (diagnosis), Carcinoma, Embryonal (genetics), Epidermal Growth Factor (biosynthesis), Epidermal Growth Factor (genetics), Epigenesis, Genetic, GPI-Linked Proteins (biosynthesis), GPI-Linked Proteins (genetics), Gene Expression Regulation, Neoplastic, Humans, Intercellular Signaling Peptides and Proteins (biosynthesis), Intercellular Signaling Peptides and Proteins (genetics), Male, Membrane Glycoproteins (biosynthesis), Membrane Glycoproteins (genetics), Mice, Mice, Transgenic, Neoplasm Proteins (biosynthesis), Neoplasm Proteins (genetics), Testicular Neoplasms (blood), Testicular Neoplasms (diagnosis), Testicular Neoplasms (genetics).
- MESH :
- chemical , biosynthesis : Epidermal Growth Factor, GPI-Linked Proteins, Intercellular Signaling Peptides and Proteins, Membrane Glycoproteins, Neoplasm Proteins.
- blood : Carcinoma, Embryonal, Testicular Neoplasms.
- diagnosis : Carcinoma, Embryonal, Testicular Neoplasms.
- genetics : Carcinoma, Embryonal, Epidermal Growth Factor, GPI-Linked Proteins, Intercellular Signaling Peptides and Proteins, Membrane Glycoproteins, Neoplasm Proteins, Testicular Neoplasms.
- Animals, Epigenesis, Genetic, Gene Expression Regulation, Neoplastic, Humans, Male, Mice, Mice, Transgenic.
Abstract
Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co‐receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non‐seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non‐seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.
Url:
DOI: 10.1016/j.molonc.2015.11.003
PubMed: 26654129
PubMed Central: 5423140
Affiliations:
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Le document en format XML
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J." last="Looijenga">Leendert H. J. Looijenga</name><affiliation><nlm:aff id="mol22016104526-aff-0002"></nlm:aff></affiliation></author></analytic><series><title level="j">Molecular Oncology</title><idno type="ISSN">1574-7891</idno><idno type="eISSN">1878-0261</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Carcinoma, Embryonal (blood)</term><term>Carcinoma, Embryonal (diagnosis)</term><term>Carcinoma, Embryonal (genetics)</term><term>Epidermal Growth Factor (biosynthesis)</term><term>Epidermal Growth Factor (genetics)</term><term>Epigenesis, Genetic</term><term>GPI-Linked Proteins (biosynthesis)</term><term>GPI-Linked Proteins (genetics)</term><term>Gene Expression Regulation, Neoplastic</term><term>Humans</term><term>Intercellular Signaling Peptides and Proteins (biosynthesis)</term><term>Intercellular Signaling Peptides and Proteins (genetics)</term><term>Male</term><term>Membrane Glycoproteins (biosynthesis)</term><term>Membrane Glycoproteins (genetics)</term><term>Mice</term><term>Mice, Transgenic</term><term>Neoplasm Proteins (biosynthesis)</term><term>Neoplasm Proteins (genetics)</term><term>Testicular Neoplasms (blood)</term><term>Testicular Neoplasms (diagnosis)</term><term>Testicular Neoplasms (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Carcinome embryonnaire (diagnostic)</term><term>Carcinome embryonnaire (génétique)</term><term>Carcinome embryonnaire (sang)</term><term>Facteur de croissance épidermique (biosynthèse)</term><term>Facteur de croissance épidermique (génétique)</term><term>Glycoprotéines membranaires (biosynthèse)</term><term>Glycoprotéines membranaires (génétique)</term><term>Humains</term><term>Mâle</term><term>Protéines et peptides de signalisation intercellulaire (biosynthèse)</term><term>Protéines et peptides de signalisation intercellulaire (génétique)</term><term>Protéines liées au GPI (biosynthèse)</term><term>Protéines liées au GPI (génétique)</term><term>Protéines tumorales (biosynthèse)</term><term>Protéines tumorales (génétique)</term><term>Régulation de l'expression des gènes tumoraux</term><term>Souris</term><term>Souris transgéniques</term><term>Tumeurs du testicule (diagnostic)</term><term>Tumeurs du testicule (génétique)</term><term>Tumeurs du testicule (sang)</term><term>Épigenèse génétique</term></keywords><keywords scheme="MESH" type="chemical" qualifier="biosynthesis" xml:lang="en"><term>Epidermal Growth Factor</term><term>GPI-Linked Proteins</term><term>Intercellular Signaling Peptides and Proteins</term><term>Membrane Glycoproteins</term><term>Neoplasm Proteins</term></keywords><keywords scheme="MESH" qualifier="biosynthèse" xml:lang="fr"><term>Facteur de croissance épidermique</term><term>Glycoprotéines membranaires</term><term>Protéines et peptides de signalisation intercellulaire</term><term>Protéines liées au GPI</term><term>Protéines tumorales</term></keywords><keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Carcinoma, Embryonal</term><term>Testicular Neoplasms</term></keywords><keywords scheme="MESH" qualifier="diagnosis" xml:lang="en"><term>Carcinoma, Embryonal</term><term>Testicular Neoplasms</term></keywords><keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr"><term>Carcinome embryonnaire</term><term>Tumeurs du testicule</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Carcinoma, Embryonal</term><term>Epidermal Growth Factor</term><term>GPI-Linked Proteins</term><term>Intercellular Signaling Peptides and Proteins</term><term>Membrane Glycoproteins</term><term>Neoplasm Proteins</term><term>Testicular Neoplasms</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Carcinome embryonnaire</term><term>Facteur de croissance épidermique</term><term>Glycoprotéines membranaires</term><term>Protéines et peptides de signalisation intercellulaire</term><term>Protéines liées au GPI</term><term>Protéines tumorales</term><term>Tumeurs du testicule</term></keywords><keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Carcinome embryonnaire</term><term>Tumeurs du testicule</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Epigenesis, Genetic</term><term>Gene Expression Regulation, Neoplastic</term><term>Humans</term><term>Male</term><term>Mice</term><term>Mice, Transgenic</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Humains</term><term>Mâle</term><term>Régulation de l'expression des gènes tumoraux</term><term>Souris</term><term>Souris transgéniques</term><term>Épigenèse génétique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Type II germ cell tumors arise after puberty from a germ cell that was incorrectly programmed during fetal life. Failure of testicular germ cells to properly differentiate can lead to the formation of germ cell neoplasia in situ of the testis; this precursor cell invariably gives rise to germ cell cancer after puberty. The Nodal co‐receptor Cripto is expressed transiently during normal germ cell development and is ectopically expressed in non‐seminomas that arise from germ cell neoplasia in situ, suggesting that its aberrant expression may underlie germ cell dysregulation and hence germ cell cancer. Here we investigated methylation of the Cripto promoter in mouse germ cells and human germ cell cancer and correlated this with the level of CRIPTO protein expression. We found hypomethylation of the CRIPTO promoter in undifferentiated fetal germ cells, embryonal carcinoma and seminomas, but hypermethylation in differentiated fetal germ cells and the differentiated types of non‐seminomas. CRIPTO protein was strongly expressed in germ cell neoplasia in situ along with embryonal carcinoma, yolk sac tumor and seminomas. Further, cleaved CRIPTO was detected in media from seminoma and embryonal carcinoma cell lines, suggesting that cleaved CRIPTO may provide diagnostic indication of germ cell cancer. Accordingly, CRIPTO was detectable in serum from 6/15 patients with embryonal carcinoma, 5/15 patients with seminoma, 4/5 patients with germ cell neoplasia in situ cells only and in 1/15 control patients. These findings suggest that CRIPTO expression may be a useful serological marker for diagnostic and/or prognostic purposes during germ cell cancer management.</p></div></front></TEI><affiliations><list></list><tree><noCountry><name sortKey="Bowles, Josephine" sort="Bowles, Josephine" uniqKey="Bowles J" first="Josephine" last="Bowles">Josephine Bowles</name><name sortKey="Burnet, Guillaume" sort="Burnet, Guillaume" uniqKey="Burnet G" first="Guillaume" last="Burnet">Guillaume Burnet</name><name sortKey="Gillis, Ad J M" sort="Gillis, Ad J M" uniqKey="Gillis A" first="Ad J. M." last="Gillis">Ad J. M. Gillis</name><name sortKey="Koopman, Peter" sort="Koopman, Peter" uniqKey="Koopman P" first="Peter" last="Koopman">Peter Koopman</name><name sortKey="Looijenga, Leendert H J" sort="Looijenga, Leendert H J" uniqKey="Looijenga L" first="Leendert H. J." last="Looijenga">Leendert H. J. Looijenga</name><name sortKey="Spiller, Cassy M" sort="Spiller, Cassy M" uniqKey="Spiller C" first="Cassy M." last="Spiller">Cassy M. Spiller</name><name sortKey="Stoop, Hans" sort="Stoop, Hans" uniqKey="Stoop H" first="Hans" last="Stoop">Hans Stoop</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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