Disease relevance of Tdgf1

• Tdgf1 corresponds to the gene expressed in F9 teratocarcinoma cells [1].
• The cripto peptides were tested for their ability to stimulate MAP-kinase activity, for inhibition of beta-casein induction, and for Shc phosphorylation in MDA-MB 453 human mammary carcinoma cells and HC-11 mouse mammary epithelial cells [2].
• Cr-1/CR-1 is overexpressed in mouse and human mammary tumors and inappropriate overexpression of Cr-1 in mouse mammary epithelial cells can lead to the clonal expansion of ductal hyperplasias [3].
• cripto is a gene encoding an epidermal growth factor-related protein that is expressed in undifferentiated embryonal carcinoma cells [4].
• To ascertain if cripto is capable of functioning as a transforming gene, a full-length human cripto complementary DNA under the transcriptional control of the Rous sarcoma virus long terminal repeat has been cotransfected with the selectable pSV2neo marker plasmid into immortalized mouse NOG-8 mammary epithelial cells [4].

Psychiatry related information on Tdgf1

• The long latency period suggests that additional genetic alterations are required to facilitate mammary tumor formation in conjunction with CR-1 [5].

High impact information on Tdgf1

• Before gastrulation, Cripto is asymmetrically expressed in a proximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm [6].
• A substantial proportion of FoxH1(-/-) embryos failed to orient the anterior-posterior (A-P) axis correctly, as do mice lacking Cripto, a coreceptor for Nodal [7].
• MSP also caused phagocytosis via the C3b receptor, CR1 [8].
• Thus, MSP causes direct or indirect activation of two receptors of the mouse resident peritoneal macrophage, CR1 and the C5a receptor [8].
• 7G6 was able to downregulate CR1 and CR2 on the surface of B cells and, in addition, to inhibit rosette formation with C3d-coated sheep erythrocytes (EC3d) [9].

Biological context of Tdgf1

• Analysis of their DNA coding region provided no evidence that Tdgf1 could be the responsible gene for these phenotypes [1].
• During organogenesis, Cripto localized to the developing heart [10].
• In situ hybridization analysis during murine embryogenesis (day 6.2 to day 10.5) reveals a very restricted expression pattern. cripto transcripts are first detected in a few epiblastic cells at day 6 [11].
• The murine cripto gene: expression during mesoderm induction and early heart morphogenesis [11].
• 5. During gastrulation, the transcripts are expressed in the forming mesoderm and later during development cripto gene expression is restricted to the truncus arteriosus of the developing heart [11].

Anatomical context of Tdgf1

• Teratocarcinoma-derived growth factor-1 (Tdgf1), a member of the "EGF family" of growth factors, is expressed during mouse gastrulation in the forming mesoderm and later in the truncus arteriosus of the developing heart [1].
• TGF alpha, CR-1, and AR transcripts were detected in all of the mammary glands assayed [12].
• CR-1 mRNA level increased with age and was detected primarily in epithelium, with some scattered expression in adjacent stroma [12].
• In situ hybridization studies of the implanting embryo revealed Cripto expression localized to the entire ectoderm and then to the rapidly growing ectoplacental cone [10].
• During gastrulation in the mouse, cripto-encoding transcripts are expressed in the forming mesoderm and later in the truncus arteriosus of the developing heart [13].

Associations of Tdgf1 with chemical compounds

• These data demonstrate that the CR-1 is a glycoprotein that can function as a growth factor through an EGF receptor-independent pathway [14].
• Monensin or tunicamycin treatment resulted in a shift of the 27-29-kDa human CR-1 protein to 24 kDa and 20 kDa, respectively [14].
• Several neomycin-resistant clones were isolated that express high levels of a specific cripto 4.5-kilobase mRNA transcript and possess multiple copies of cripto plasmid DNA [4].
• Mutations in the CR1 and CR2 domains have opposing effects on ligand binding affinity, receptor dimerization, tyrosine kinase activation, and signaling competence [15].
• The present study demonstrates that CR-1 indirectly induces tyrosine phosphorylation of erb B-4 but not of the epidermal growth factor-related receptors erb B-2 and erb B-3 in different mouse and human mammary epithelial cell lines [16].

Regulatory relationships of Tdgf1

• Cripto is also expressed in explants treated with bone morphogenetic protein 4 (BMP4) [17].
• Beta-catenin regulates Cripto- and Wnt3-dependent gene expression programs in mouse axis and mesoderm formation [18].
• The present study demonstrates that CR-1 can induce apoptosis in HC-11 mouse mammary epithelial cells, as measured by bis-benzimide stained nuclei, TUNEL assay and cell death ELISA [19].
• These studies suggest that CR-1 promotes apoptosis by mediating the induction of caspase-3-like protease and downregulating the expression of Bcl-xL [19].
• In addition, CR-1 that had been purified from human milk is able to stimulate the phosphorylation of mitogen activated protein kinase in nontransformed NMuMG mouse mammary epithelial cells [20].

Other interactions of Tdgf1

• We also found intense CR-1 and AR mRNA expression and strong immunoreactivity in seven different carcinogen-induced and eight spontaneous mammary tumors [12].
• Cripto-1 (CR-1, human; Cr-1, mouse)--also known as teratocarcinoma-derived growth factor-1--is a novel EGF-related protein that induces branching morphogenesis in mammary epithelial cells both in vitro and in vivo and inhibits the expression of various milk proteins [3].
• But recombinant mature Nodal, unlike uncleaved precursor, can efficiently rescue Cripto expression [17].
• Complementary functions of Otx2 and Cripto in initial patterning of mouse epiblast [21].
• In vitro differentiated mouse embryonic stem (ES) cells with deletion of the TGF-beta pathway-related factors Smad4 or Cripto exhibited increased numbers of neurons [22].

Analytical, diagnostic and therapeutic context of Tdgf1

• A specific 36-kDa immunoreactive protein was detected by Western blot analysis in human cell lines that express CR-1 mRNA but not in cell lines that fail to express this transcript [14].
• By means of immunofluorescence analysis and biochemical characterization, we show that Cripto is a membrane-bound protein anchored to the lipid bilayer by a glycosylphosphatidylinositol (GPI) moiety [23].
• In the present study, we have screened the expression of CR-1 mRNA and protein in a wide panel of human cancer cell lines by using reverse transcriptase (RT)-PCR, real-time PCR and immunocytochemistry [24].
• Cripto: a novel target for antibody-based cancer immunotherapy [25].
• Chimeric mice were constructed by microinjection of double targeted Cr1(-/- )embryonic stem cells into normal C57BL/6 blastocysts [26].

References