Disease relevance of Tgfa

• This region has recently been shown to contain a binding region of TGF-alpha for the EGF receptor, and this raises the question of whether vaccinia virus utilizes the EGF receptor in order to bind to and infect cells [1].
• In addition, adult transgenic skin that was still both sensitive to TGF-alpha and subject to mild irritation displayed localized regions of leukocytic infiltration and granular layer loss, characteristics frequently seen in psoriasis in humans [2].
• Transgenic mice overexpressing TGF-alpha develop tissue changes in the pancrease resembling changes found in chronic pancreatitis [3].
• To test this hypothesis, we interbred separate transgenic strains harboring either a mouse mammary tumor virus/TGF-alpha or a mouse mammary tumor virus/neu transgene to generate bitransgenic mice that coexpress TGF-alpha and neu in the mammary epithelium [4].
• Autonomous growth in serum-free medium and production of hepatocellular carcinomas by differentiated hepatocyte lines that overexpress transforming growth factor alpha 1 [5].

Psychiatry related information on Tgfa

• Female mice coexpressing TGF-alpha and neu developed multifocal mammary tumors which arose after a significantly shorter latency period than either parental strain alone [4].
• To study the role of EGF, TGF-alpha and EGFR in early human development, two methods applicable for analysis of expression at the single embryo level have been employed [6].
• TGF-alpha is expressed rhythmically in the SCN, and when infused into the third ventricle it reversibly inhibited locomotor activity and disrupted circadian sleep-wake cycles [7].

High impact information on Tgfa

• Crystal structure of a truncated epidermal growth factor receptor extracellular domain bound to transforming growth factor alpha [8].
• The phenotype of TGF alpha -/- mice is remarkably similar to that of the mouse mutant waved-1 (wa-1) [9].
• Although TGF alpha deficiency affected skin and eyes, wound healing in these tissues was not impaired [10].
• TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice [10].
• To explore the physiological roles of transforming growth factor alpha (TGF alpha), we disrupted the mouse gene by homologous recombination in embryonic stem cells [10].

Chemical compound and disease context of Tgfa

• Wild-genotype mice had significantly higher lung fibrosis scores at Days 7 and 14 after bleomycin treatment than did TGF-alpha-deficient animals [11].
• Transforming growth factor-alpha (TGF alpha)-pseudomonas exotoxin-40 (PE40) is a chimeric protein consisting of an N-terminal TGF alpha domain fused to a C-terminal 40-kDa segment of the pseudomonas exotoxin A protein [12].
• The induction of cleft palate (CP) by all trans-retinoic acid (RA) was associated with altered expression of TGFalpha, EGF receptor, and binding of EGF [13].
• Abrogation of transforming growth factor-alpha/epidermal growth factor receptor autocrine signaling by an RXR-selective retinoid (LGD1069, Targretin) in head and neck cancer cell lines [14].
• Phenobarbital promotes liver growth in c-myc/TGF-alpha transgenic mice by inducing hypertrophy and inhibiting apoptosis [15].

Biological context of Tgfa

• Binding of EGF or of transforming growth factor-alpha (TGF-alpha) or other related factors activates the receptor and induces cell proliferation and differentiation [16].
• The conserved sequence includes a region of high homology (6 out of 10 amino acids) from residues 71 to 80, corresponding to the third disulphide loop of both EGF and TGF-alpha [1].
• BACKGROUND: Epidermal growth factor (EGF)-related proteins, such as transforming growth factor-alpha (TGF-alpha), control cancer cell growth through hormonal pathways (i.e., autocrine [hormone acts on cell that produces it] and paracrine [hormone acts on nearby cells] pathways) [17].
• In order to investigate the mechanisms by which TGF-alpha contributes to hepatocyte replication and transformation, we isolated hepatocytes from mice bearing a human TGF-alpha transgene and examined their growth properties and gene expression in defined, serum-free culture [5].
• Using keratinocytes isolated from mice with genetic defects in TGF alpha expression, we tested whether TGF alpha is required for transformation by the v-rasHa oncogene [18].

Anatomical context of Tgfa

• Transforming growth factor-alpha (TGF-alpha) and its sheddase, TACE (also known as ADAM17), were induced by AngII treatment, TACE was redistributed to apical membranes and EGFR was phosphorylated [19].
• Unexpectedly, the only regions of epidermis especially responsive to TGF-alpha overexpression were those that were normally thick and where hair follicle density was typically low [2].
• Growth retardation, duodenal lesions, and aberrant ileum architecture in triple null mice lacking EGF, amphiregulin, and TGF-alpha [20].
• Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice [4].
• The bivalent forms of MAb could inhibit proliferation stimulated by endogenous (autocrine) TGF-alpha in cultures of these three cell lines [21].

Associations of Tgfa with chemical compounds

• Mice heterozygous for the N-ethyl-N-nitrosourea-induced Waved-5 (Wa5) mutation, isolated in a screen for dominant, visible mutations, exhibit a wavy coat similar to mice homozygous for the recessive Tgfa wa1 or Egfr wa2 alleles [22].
• Pharmacologic inhibition of AngII prevented TGF-alpha and TACE accumulation as well as renal lesions after nephron reduction [19].
• We found that EGF continues to stimulate maximal tyrosine phosphorylation of EGFR following internalization, while, as expected, TGFalpha stimulates markedly less [23].
• The half-life of TGF-alpha mRNA is 40-60 min in antisense cells and more than 8 h in parental KB cells, as determined by actinomycin D decay curves [24].
• The resulting higher level of receptor activation by EGF, however, did not yield higher levels of phosphatidylinositol (4,5)-bisphosphate (PIP2) hydrolysis over those stimulated by TGFalpha [23].

Physical interactions of Tgfa

• Contribution of the transforming growth factor alpha B-loop beta-sheet to binding and activation of the epidermal growth factor receptor [25].
• The c-myc oncogene is commonly amplified in breast cancer and is known to interact synergistically with transforming growth factor alpha (TGF alpha) in vitro to promote phenotypic transformation of mammary epithelial cells [26].
• Since TGF-alpha binds to the epidermal growth factor (EGF)-receptor, this action may be exerted through this receptor [27].
• In addition, in vitro analysis revealed that biglycan binds to TGF-alpha, thus interrupting EGFR signaling pathways essential for mesenchymal cell migration induced by eyelid epithelium [28].
• The potential regulatory role of CBP/p300-interacting transactivators with glutamic acid/aspartic acid-rich carboxyl-terminal domain in the transcription of genes like TGF-alpha implicates the protein in diurnal activity rhythms [29].

Enzymatic interactions of Tgfa

• The PKCdelta that was tyrosine-phosphorylated in response to TGFalpha had reduced activity compared with the nontyrosine-phosphorylated PKCdelta [30].
• The neurotrophic actions of HB-EGF and TGFalpha are accompanied by an elevation in immunoreactive dual phosphorylated mitogen-activated protein kinase (MAP kinase) in neurons, providing evidence that the MAP kinase cascade mediates these actions [31].

Regulatory relationships of Tgfa

• These findings indicate that TGF alpha is not essential for epidermal neoplasia induced by the v-rasHa oncogene and suggest that another EGF family member(s) may contribute to autocrine growth stimulation of ras-transformed keratinocytes [18].
• Enhanced sensitivity to tumor growth and development in multistage skin carcinogenesis by transforming growth factor-alpha-induced epidermal growth factor receptor activation but not p53 inactivation [32].
• This suggests that TGFalpha-induced tyrosine phosphorylation of PKC delta results from the activation of a tyrosine kinase rather than physical association of PKCdelta with a membrane-anchored tyrosine kinase [30].
• Transforming growth factor alpha up-regulates desmin expression during embryonic mouse tongue myogenesis [33].
• The aim of this study was to determine whether transforming growth factor-alpha (TGF-alpha) regulates expression of mouse placental lactogen-I (mPL-I) and mPL-II at midpregnancy in vitro [34].

Other interactions of Tgfa

• Autocrine transforming growth factor alpha is dispensible for v-rasHa-induced epidermal neoplasia: potential involvement of alternate epidermal growth factor receptor ligands [18].
• IGF-I also exerted its effect predominantly in the upper crypt, while TGF alpha raised proliferation at all cell positions [35].
• We have synthesized novel, antisense mixed backbone oligonucleotides (AS MBOs) directed against TGFalpha, AR and CR [36].
• In early embryos, TNF induces apoptosis, whereas TGFA could act as a survival factor [37].
• The number of colonies increased significantly when EGF, but not TGF-alpha, was used in combination with bFGF [38].

Analytical, diagnostic and therapeutic context of Tgfa

• Amplification of embryonic day 14 striatal mRNA by using reverse transcription/PCR revealed mRNAs for EGF, TGF alpha, and the EGF receptor [39].
• They also blocked growth stimulation by added exogenous TGF-alpha in cultures of MCF10A cells and the growth-inhibitory effect of exogenous TGF-alpha upon MDA468 and A431 cell cultures [21].
• The developmental expression of TGF-alpha and its receptor, the epidermal growth factor receptor (EGFR), in whole testis and isolated cell types was determined using a nuclease protection assay [40].
• Synthesis and secretion of TGF-alpha by HSC-43 cells were confirmed by biological assay and enzyme-linked immunosorbent assay [41].
• To assess a possible functional redundancy among TGF-alpha-related ligands in response to a nerve injury, mRNA expression of the EGF family was analyzed by RT-PCR in L4/L5 DRG pools and distal degenerating sciatic nerve segments after sciatic nerve ligation [42].

References