Assignment of human teratocarcinoma derived growth factor (TDGF) sequences to chromosomes 2q37, 3q22, 6p25 and 19q13.1

Scognamiglio, B.; Baldassarre, Gustavo; Cassano, C.; Tucci, Marina; Montuori, Nunzia; Dono, Rosanna; Lembo, Gaia; Barra, Adriano; Lago, C. T.; Viglietto, Giuseppe; Rocchi, Mariano; Persico, M. Graziella

doi:10.1159/000015263

Cited by 13 publications

(10 citation statements)

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“…4B). The autosomal gene CRIPTO-1 has a highly homologous sequence on the X chromosome termed CRIPTO-3, which is currently believed to be a processed pseudogene (31). Interestingly, in addition to the CRIPTO-3 open reading frame, 0.7 kb of the upstream region is highly homologous to the CRIPTO-1 promoter.…”

Section: Gcnf Binds To the Cripto-1 Promoter In Vitro-gcnfmentioning

confidence: 99%

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Germ Cell Nuclear Factor Is a Repressor of CRIPTO-1 and CRIPTO-3

Hentschke

Kurth

Borgmeyer

et al. 2006

Journal of Biological Chemistry

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The pluripotency of embryonic stem and embryonic carcinoma cells is maintained by the expression of a set of "stemness" genes. Whereas these genes are down-regulated upon induction of differentiation, the germ cell nuclear factor (GCNF) is transiently up-regulated and represses several pluripotency genes. CRIPTO-1, a co-receptor for the morphogen nodal, is strongly expressed in undifferentiated cells and is rapidly down-regulated during retinoic acid-induced differentiation. Although CRIPTO-1 is expressed at very low levels in adult tissues under normal conditions, it is found highly expressed in a broad range of tumors, where it acts as a potent oncogene. We show that expression of CRIPTO-1 is directly repressed by GCNF during differentiation of the human teratocarcinoma cell line, NT2. GCNF bound to a DR0 element of the CRIPTO-1 promoter in vitro, as shown by electrophoretic mobility shift assays, and in vivo, as demonstrated by chromatin immunoprecipitation. Reporter gene assays demonstrated that GCNF-mediated repression of the CRIPTO-1 promoter is dependent upon the DR0 site. Overexpression of GCNF in NT2 cells resulted in repression of CRIPTO-1 transcription, whereas expression of the transcription-activating fusion construct GCNF-VP16 led to an induction of the CRIPTO-1 gene and prevented its retinoic acidinduced down-regulation. Furthermore, we demonstrated that CRIPTO-3, a processed pseudogene of CRIPTO-1 on the X chromosome, is expressed in undifferentiated NT2 cells and is regulated by GCNF in parallel to CRIPTO-1. Thus, our study supports the hypothesis of GCNF playing a central role during differentiation of stem cells by repression of stem cell-specific genes.

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Section: Gcnf Binds To the Cripto-1 Promoter In Vitro-gcnfmentioning

confidence: 99%

“…24). Several pseudogenes of CRIPTO-1 reside in the human genome (31). One of these, CRIPTO-3 is located on the X chromosome and retains an open reading frame as well as a portion of the promoter region of CRIPTO-1 (32).…”

mentioning

confidence: 99%

Germ Cell Nuclear Factor Is a Repressor of CRIPTO-1 and CRIPTO-3

Hentschke

Kurth

Borgmeyer

et al. 2006

Journal of Biological Chemistry

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“…These data suggest that regulation of expression of the mouse and human cripto genes may not be entirely similar. Multiple copies of cripto-specific sequences are present in the human and mouse genomes (Dono et al 1991, Saccone et al 1995, Liguori et al 1996, Scognamiglio et al 1999. At least five other human CR-1-related pseudogenes and two mouse Cr-1 pseudogenes have been identified (Scognamiglio et al 1999).…”

Section: Genomic Organization Of Mouse and Human Criptomentioning

confidence: 99%

“…Multiple copies of cripto-specific sequences are present in the human and mouse genomes (Dono et al 1991, Saccone et al 1995, Liguori et al 1996, Scognamiglio et al 1999. At least five other human CR-1-related pseudogenes and two mouse Cr-1 pseudogenes have been identified (Scognamiglio et al 1999). The CR-2, CR-4 and CR-5 genes are truncated at the 5′-end and have accumulated point mutations, deletions and insertions (Scognamiglio et al 1999).…”

Section: Genomic Organization Of Mouse and Human Criptomentioning

confidence: 99%

“…At least five other human CR-1-related pseudogenes and two mouse Cr-1 pseudogenes have been identified (Scognamiglio et al 1999). The CR-2, CR-4 and CR-5 genes are truncated at the 5′-end and have accumulated point mutations, deletions and insertions (Scognamiglio et al 1999). These genes map to chromosomes 2q37, 6p25 and 3q22 respectively while CR-6 maps to 19q13.1.…”

Section: Genomic Organization Of Mouse and Human Criptomentioning

confidence: 99%

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The EGF-CFC family: novel epidermal growth factor-related proteins in development and cancer.

Saloman

Bianco

Ebert

et al. 2000

Endocrine-Related Cancer

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112

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The EGF-CFC gene family encodes a group of structurally related proteins that serve as important competence factors during early embryogenesis in Xenopus, zebrafish, mice and humans. This multigene family consists of Xenopus FRL-1, zebrafish one-eyed-pinhead (oep), mouse cripto (Cr-1) and cryptic, and human cripto (CR-1) and criptin. FRL-1, oep and mouse cripto are essential for the formation of mesoderm and endoderm and for correct establishment of the anterior/ posterior axis. In addition, oep and cryptic are important for the establishment of left-right (L/R) asymmetry. In zebrafish, there is strong genetic evidence that oep functions as an obligatory co-factor for the correct signaling of a transforming growth factor-β (TGFβ)-related gene, nodal, during gastrulation and during L/R asymmetry development. Expression of Cr-1 and cryptic is extinguished in the embryo after day 8 of gestation except for the developing heart where Cr-1 expression is necessary for myocardial development. In the mouse, cryptic is not expressed in adult tissues whereas Cr-1 is expressed at a low level in several different tissues including the mammary gland. In the mammary gland, expression of Cr-1 in the ductal epithelial cells increases during pregnancy and lactation and immunoreactive and biologically active Cr-1 protein can be detected in human milk. Overexpression of Cr-1 in mouse mammary epithelial cells can facilitate their in vitro transformation and in vivo these Cr-1-transduced cells produce ductal hyperplasias in the mammary gland. Recombinant mouse or human cripto can enhance cell motility and branching morphogenesis in mammary epithelial cells and in some human tumor cells. These effects are accompanied by an epithelial-mesenchymal transition which is associated with a decrease in β-catenin function and an increase in vimentin expression. Expression of cripto is increased several-fold in human colon, gastric, pancreatic and lung carcinomas and in a variety of different types of mouse and human breast carcinomas. More importantly, this increase can first be detected in premalignant lesions in some of these tissues. Although a specific receptor for the EGF-CFC proteins has not yet been identified, oep depends upon an activin-type RIIB and RIB receptor system that functions through Smad-2. Mouse and human cripto have been shown to activate a ras/raf/MAP kinase signaling pathway in mammary epithelial cells. Activation of phosphatidylinositol 3-kinase and Akt are also important for the ability of CR-1 to stimulate cell migration and to block lactogenic hormone-induced expression of β-casein and whey acidic protein.In mammary epithelial cells, part of these responses may depend on the ability of CR-1 to transactivate erb B-4 and/or fibroblast growth factor receptor 1 through an src-like tyrosine kinase.

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