Immunohistochemical Detection of Cripto-1, Amphiregulin and Transforming Growth-Factor-Alpha in Human Gastric Carcinomas and Intestinal Metaplasias

Sendo, Toshiaki; Salomon, David; Normanno, Nicola; Johnson, Gibbes R.; Gullick, W. J.; Mandai, Koichi; Moriwaki, Shogo; Takashima, Shinogu; Kuniyasu, M.; Tahara, Eiichi; Kawami, Hiroyuki; Nishiyama, Masahiko; Toge, Tetsuya

doi:10.3892/ijo.5.2.215

Cited by 12 publications

(16 citation statements)

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“…Furthermore, CR-1 expression is significantly increased in premalignant lesions, such as colon adenomas, intestinal metaplasia of the gastric mucosa and ductal carcinoma in situ (DCIS) of the breast. In this respect, the frequency of CR-1 expression in the adenomas was found to correlate directly with the degree of dysplasia, and with the size and the histological subtype of colon adenomas (Saeki et al, 1994b). CR-1 expression was also detected in 62% of normal colon mucosa specimens from individuals that belong to families with a high incidence of colorectal carcinomas, whereas only 20% of colon mucosa from low-risk patient specimens was positive for CR-1 (De Angelis et al, 1999).…”

Section: In Vivo Tumorigenesis Induced By Cripto-1mentioning

confidence: 89%

Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

et al. 2005

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It is increasingly evident that genes known to perform critical roles during early embryogenesis, particularly during stem cell renewal, pluripotentiality and survival, are also expressed during the development of cancer. In this regard, oncogenesis may be considered as the recapitulation of embryogenesis in an inappropriate temporal and spatial manner. The epidermal growth factor-Cripto-1/FRL1/cryptic family of proteins consists of extracellular and cell-associated proteins that have been identified in several vertebrate species. During early embryogenesis, epidermal growth factor-Cripto-1/FRL1/ cryptic proteins perform an obligatory role as coreceptors for the transforming growth factor-beta subfamily of proteins, which includes Nodal. Cripto-1 has also been shown to function as a ligand through a Nodal/Alk4-independent signaling pathway that involves binding to glypican-1 and the subsequent activation through src of phosphoinositol-3 kinase/Akt and ras/mitogen-activated protein kinase intracellular pathways. Expression of Cripto-1 is increased in several human cancers and its overexpression is associated with the development of mammary tumors in mice. Here, we review the role of Cripto-1 during embryogenesis, cell migration, invasion and angiogenesis and how these activities may relate to cellular transformation and tumorigenesis. We also briefly discuss evidence suggesting that Cripto-1 may be involved in stem cell maintenance.

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Section: In Vivo Tumorigenesis Induced By Cripto-1mentioning

confidence: 89%

Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

et al. 2005

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“…An increase in CR-1 expression has been observed in 53% of premalignant lesions of the stomach, such as intestinal metaplasia of the gastric mucosa, in gastric adenomas, and in 46% of early and advanced gastric carcinomas (Kuniyasu et al 1991, Saeki et al 1994a. Interestingly, the incidence of CR-1 expression was found to correlate with the degree of dysplasia in the intestinal metaplasia and with tumor stage and patient prognosis in gastric cancer (Kuniyasu et al 1994, Allgayer et al 1997).…”

Section: Gastric Cancermentioning

confidence: 99%

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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123

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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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“…AR expression can be induced by phorbol ester (7,25), estrogen (25,26), androgen (27), and other EGFR ligands, such as EGF, TGF-␣ and heparin-binding EGF-like growth factor (22,23,28). Overexpression of AR is often observed in human cancers of the breast (24), colon (10,21), stomach (22,29,30), and pancreas (16,23). Furthermore, in human pancreatic cancer AR expression correlates with decreased patient survival (16).…”

mentioning

confidence: 99%

COOH-terminal Extended Recombinant Amphiregulin with Bioactivity Comparable with Naturally Derived Growth Factor

Thompson¹,

Harris

Hoang³

et al. 1996

Journal of Biological Chemistry

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The mature secreted form of the epidermal growth factor (EGF) receptor ligand amphiregulin (AR) is reported to be an 84-amino acid residue polypeptide, which is generated by proteolytic processing of a 252-amino acid precursor. This form of recombinant AR (rAR84) and two forms with COOH-terminal extensions corresponding to sequences from the AR precursor (rAR87 and rAR92) were expressed at high levels in Escherichia coli, oxidized to the correct disulfide arrangement, and purified to homogeneity. rAR84 competed poorly for binding of radiolabeled EGF to the EGF receptor and had little ability to stimulate growth of Balb/c/3T3 cells. In striking contrast, rAR87 and rAR92 possessed 42-and 20-fold greater receptor binding activity and 55-and 14-fold greater bioactivity, respectively. Furthermore, addition of the COOH-terminal four amino acids from transforming growth factor ␣ to the COOH terminus of rAR84 improved the activity of rAR84 by 100-and 1000-fold, respectively, in these assays. rAR87 was found to have ϳ32% of the specific activity of natural AR from MCF-7 cells when compared in two different bioassays. These findings strongly suggest that the 84-amino acid sequence is not the correct structure of the naturally occurring secreted form of AR and that natural AR contains additional amino acid residues at the COOH-terminal end.

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Immunohistochemical Detection of Cripto-1, Amphiregulin and Transforming Growth-Factor-Alpha in Human Gastric Carcinomas and Intestinal Metaplasias

Cited by 12 publications

References 0 publications

Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

Cripto-1: a multifunctional modulator during embryogenesis and oncogenesis

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

COOH-terminal Extended Recombinant Amphiregulin with Bioactivity Comparable with Naturally Derived Growth Factor

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