The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TGFA  -  transforming growth factor, alpha

Homo sapiens

Synonyms: Protransforming growth factor alpha
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TGFA


Psychiatry related information on TGFA

  • Here we assess possible interaction between the child's TGFA TaqI A2A2 genotype and maternal cigarette smoking, alcohol consumption, use of multivitamins and folic acid [4].
  • The existence of an autocrine loop for self-stimulation of growth in malignant cells has been proposed for transforming growth factor-alpha (TGF alpha) and its receptor, the epidermal growth factor (EGF) receptor, in a variety of malignant cell types [5].
  • These findings provide evidence that TGF-alpha up-regulates TLR expression and function, augmenting host defense mechanisms at epithelial surfaces [6].

High impact information on TGFA


Chemical compound and disease context of TGFA


Biological context of TGFA

  • Significant associations with the TGFA TaqI and BamHI RFLPs were confirmed, although associations of clefting with previously reported haplotypes did not reach significance [1].
  • Here we extend our original analysis of the TGFA TaqI RFLP to two other TGFA RFLPs and seven other RFLPs at five candidate genes in 117 nonsyndromic cases of CL/P and 113 controls [1].
  • An allelic association between the transforming growth factor alpha gene (TGFA) situated in the chromosome 2p13 region and nonsyndromic cleft lip with or without cleft palate, also named orofacial cleft (OFC), was found in several population studies [15].
  • The gene for hexokinase II, HK2, has been previously mapped to human chromosome 2p13 by fluorescence in situ hybridization, and two-point linkage analysis has placed it near the locus for transforming growth factor alpha, TGFA [16].
  • Collectively, our findings indicate that disruption of the TGFA/EGFR/MAPK pathway may represent a strategy that could be exploited to manipulate prostate carcinoma growth and cell survival after irradiation [17].

Anatomical context of TGFA

  • Because EGFR and TGFA expression were routinely found in normal squamous epithelium, overexpression was considered present if greater uptake of the antibody was manifested by a deeper immunostain [18].
  • Working with a cloned cDNA probe (lambda hTGF1-10) and derivatives, we have mapped this gene (TGFA) to 2p13 with the use of somatic cell hybrids and in situ hybridization [19].
  • Using another monoclonal antibody directed to TGF-alpha, immunohistochemistry showed a different pattern of positive cells including eosinophilic precursor cells, in accordance with earlier findings in blood eosinophils [20].
  • The expression of transforming growth factor-alpha (TGF-alpha) in human differentiating leukemic cell lines and in circulating human eosinophils prompted the search for an analogous function in normal human bone marrow (BM) cells [20].
  • The presence of membrane-bound TGF-alpha on erythroblasts was confirmed by immunomagnetic cell sorting with polyclonal TGF-alpha antibodies; the recovered cells consisted almost entirely of erythroblasts [20].

Associations of TGFA with chemical compounds

  • Two potential CL +/- P susceptibility loci (CSL), transforming growth factor alpha (TGFA) and retinoic acid receptor (RARA), have been identified through association studies [21].
  • AREG and TGFA are biomarkers for Gefitinib non-responders [22].
  • The risk associated with two copies of the A2 allele at TGFA TaqI was strong among children whose mothers did not use folic acid (relative risk=4.5, 95% confidence interval=1.3-15.7), and was only marginal among children whose mothers reported using folic acid (RR=1.4, 95% CI=0.2-12.7) [4].
  • DESIGN: We examined the C2/TaqI variant of the TGFA gene in 536 patients with nonsyndromic CL/P and 412 controls [23].
  • Furthermore, the antibody neutralizing the TGF-alpha binding to an EGF receptor was able to reduce the DNA synthesis associated with the vitamin A deficiency [24].

Physical interactions of TGFA

  • This reduced binding is not due to an occupation of the receptors by TGF-alpha since the expression level of this mitogen in different KS cell lines does not correlate with their capacity to bind EGF [25].
  • Expression of wild-type EGFR ligands, such as transforming growth factor-alpha (TGF-alpha) or heparin-binding EGF (HB-EGF), is also often increased in gliomas resulting in an autocrine loop that contributes to the growth autonomy of glioma cells [26].
  • We now demonstrate that transmembrane TGF-alpha physically interacts with CD9, a protein with four membrane spanning domains that is frequently coexpressed with TGF-alpha in carcinomas [27].
  • NF-IL-6 binding to a 32P-labeled NF-IL-6 binding sequence was enhanced 20 min after TGF-alpha stimulation and returned to basal levels within 90 min, whereas NFkappaB binding activity was enhanced after 20 min and returned to normal 60 min after stimulation [28].
  • Neo transfected cells that did not express ER alpha or cells stably transfected with the DNA binding domain mutant C202R/E203V which prevents gene activation did not induce TGF alpha mRNA after either E(2) or 4-OHT treatment [29].

Enzymatic interactions of TGFA

  • Accompanying the increase in KGF there was also an increase in TGF-alpha precursor proteins in the culture supernatants and the phosphorylated form of the EGFR receptor was also detected in the tissue [30].
  • Tumor necrosis factor alpha-converting enzyme (TACE) is reported to cleave precursor of TGF-alpha, with release of soluble mature TGF-alpha in various epithelial tissues [31].
  • ADAM 10 correctly cleaves peptides and a soluble form of precursor TGF-alpha (proTGFecto) at the N-terminal site but not the C-terminal site [32].

Regulatory relationships of TGFA

  • The ability of TCDD to stimulate the EGFR pathway and inhibit apoptosis may be due to the ability of TCDD to increase expression of TGF-alpha, a ligand for EGFR [33].
  • IGF-1 also induced production and secretion of TGF-alpha and AR proteins as detected by immunoassays [34].
  • However, if the protein is fused with the AR heparin-binding domain, TGF-alpha secretion is inhibited unless the AR pro-region is also present [35].
  • The binding of HB-EGF to tumour cells is blocked by mAbs which act as EGF and TGF alpha antagonists [36].
  • In contrast, in HOME cells, t-PA activity and tube-like structures were induced in the presence of TGF-alpha alone, but not in the presence of HGF alone [37].

Other interactions of TGFA


Analytical, diagnostic and therapeutic context of TGFA


  1. Cleft lip with or without cleft palate: associations with transforming growth factor alpha and retinoic acid receptor loci. Chenevix-Trench, G., Jones, K., Green, A.C., Duffy, D.L., Martin, N.G. Am. J. Hum. Genet. (1992) [Pubmed]
  2. Maternal MTHFR interacts with the offspring's BCL3 genotypes, but not with TGFA, in increasing risk to nonsyndromic cleft lip with or without cleft palate. Gaspar, D.A., Matioli, S.R., de Cássia Pavanello, R., Araújo, B.C., Alonso, N., Wyszynski, D., Passos-Bueno, M.R. Eur. J. Hum. Genet. (2004) [Pubmed]
  3. Epidermal growth factor receptor (EGF-R) and transforming growth factor alpha (TGFA) expression in different endometrial cancers. Jasonni, V.M., Amadori, A., Santini, D., Ceccarelli, C., Naldi, S., Flamigni, C. Anticancer Res. (1995) [Pubmed]
  4. Cleft palate, transforming growth factor alpha gene variants, and maternal exposures: assessing gene-environment interactions in case-parent triads. Jugessur, A., Lie, R.T., Wilcox, A.J., Murray, J.C., Taylor, J.A., Saugstad, O.D., Vindenes, H.A., Abyholm, F.E. Genet. Epidemiol. (2003) [Pubmed]
  5. Modulation of EGF receptor expression by differentiating agents in human colon carcinoma cell lines. Murphy, L.D., Valverius, E.M., Tsokos, M., Mickley, L.A., Rosen, N., Bates, S.E. Cancer Commun. (1990) [Pubmed]
  6. TGF-alpha regulates TLR expression and function on epidermal keratinocytes. Miller, L.S., Sørensen, O.E., Liu, P.T., Jalian, H.R., Eshtiaghpour, D., Behmanesh, B.E., Chung, W., Starner, T.D., Kim, J., Sieling, P.A., Ganz, T., Modlin, R.L. J. Immunol. (2005) [Pubmed]
  7. EGF-R as a hemopoietic growth factor receptor: the c-erbB product is present in chicken erythrocytic progenitors and controls their self-renewal. Pain, B., Woods, C.M., Saez, J., Flickinger, T., Raines, M., Peyrol, S., Moscovici, C., Moscovici, M.G., Kung, H.J., Jurdic, P. Cell (1991) [Pubmed]
  8. Transforming growth factors beta 1 and alpha in chronic liver disease. Effects of interferon alfa therapy. Castilla, A., Prieto, J., Fausto, N. N. Engl. J. Med. (1991) [Pubmed]
  9. The TGF-alpha precursor expressed on the cell surface binds to the EGF receptor on adjacent cells, leading to signal transduction. Wong, S.T., Winchell, L.F., McCune, B.K., Earp, H.S., Teixidó, J., Massagué, J., Herman, B., Lee, D.C. Cell (1989) [Pubmed]
  10. Transmembrane TGF-alpha precursors activate EGF/TGF-alpha receptors. Brachmann, R., Lindquist, P.B., Nagashima, M., Kohr, W., Lipari, T., Napier, M., Derynck, R. Cell (1989) [Pubmed]
  11. TGF-alpha-driven tumor growth is inhibited by an EGF receptor tyrosine kinase inhibitor. El-Obeid, A., Hesselager, G., Westermark, B., Nistér, M. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  12. Retinoic acid normalizes the increased gene transcription rate of TGF-alpha and EGFR in head and neck cancer cell lines. Rubin Grandis, J., Zeng, Q., Tweardy, D.J. Nat. Med. (1996) [Pubmed]
  13. Transforming growth factor alpha-Pseudomonas exotoxin fusion protein prolongs survival of nude mice bearing tumor xenografts. Heimbrook, D.C., Stirdivant, S.M., Ahern, J.D., Balishin, N.L., Patrick, D.R., Edwards, G.M., Defeo-Jones, D., FitzGerald, D.J., Pastan, I., Oliff, A. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  14. Estrogen receptor alpha, a molecular switch converting transforming growth factor-alpha-mediated proliferation into differentiation in neuroblastoma cells. Ciana, P., Ghisletti, S., Mussi, P., Eberini, I., Vegeto, E., Maggi, A. J. Biol. Chem. (2003) [Pubmed]
  15. A locus in 2p13-p14 (OFC2), in addition to that mapped in 6p23, is involved in nonsyndromic familial orofacial cleft malformation. Pezzetti, F., Scapoli, L., Martinelli, M., Carinci, F., Bodo, M., Carinci, P., Tognon, M. Genomics (1998) [Pubmed]
  16. A novel (TA)n polymorphism in the hexokinase II gene: application to noninsulin-dependent diabetes mellitus in the Pima Indians. Ardehali, H., Tiller, G.E., Printz, R.L., Mochizuki, H., Prochazka, M., Granner, D.K. Hum. Genet. (1996) [Pubmed]
  17. Ionizing radiation-induced mitogen-activated protein (MAP) kinase activation in DU145 prostate carcinoma cells: MAP kinase inhibition enhances radiation-induced cell killing and G2/M-phase arrest. Hagan, M., Wang, L., Hanley, J.R., Park, J.S., Dent, P. Radiat. Res. (2000) [Pubmed]
  18. p53 overexpression correlates with increased survival in patients with squamous carcinoma of the tongue base. Sauter, E.R., Ridge, J.A., Gordon, J., Eisenberg, B.L. Am. J. Surg. (1992) [Pubmed]
  19. The gene for human transforming growth factor alpha is on the short arm of chromosome 2. Tricoli, J.V., Nakai, H., Byers, M.G., Rall, L.B., Bell, G.I., Shows, T.B. Cytogenet. Cell Genet. (1986) [Pubmed]
  20. Transforming growth factor-alpha (TGF-alpha) in human bone marrow: demonstration of TGF-alpha in erythroblasts and eosinophilic precursor cells and of epidermal growth factor receptors in blastlike cells of myelomonocytic origin. Walz, T.M., Malm, C., Nishikawa, B.K., Wasteson, A. Blood (1995) [Pubmed]
  21. Evidence for an association between nonsyndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4. Mitchell, L.E., Healey, S.C., Chenevix-Trench, G. Am. J. Hum. Genet. (1995) [Pubmed]
  22. Canonical WNT signaling pathway and human AREG. Katoh, Y., Katoh, M. Int. J. Mol. Med. (2006) [Pubmed]
  23. Transforming growth factor-alpha and nonsyndromic cleft lip with or without palate in Brazilian patients: results of a large case-control study. Passos-Bueno, M.R., Gaspar, D.A., Kamiya, T., Tescarollo, G., Rabanéa, D., Richieri-Costa, A., Alonso, N., Araújo, B. The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association. (2004) [Pubmed]
  24. Inhibition of epidermal growth factor-like growth factor secretion in tracheobronchial epithelial cells by vitamin A. Miller, L.A., Cheng, L.Z., Wu, R. Cancer Res. (1993) [Pubmed]
  25. Low mitogenic response to EGF and TGF-alpha: a characteristic feature of cultured Kaposi's sarcoma derived cells. Werner, S., Viehweger, P., Hofschneider, P.H., Roth, W.K. Oncogene (1991) [Pubmed]
  26. Differential gene expression analysis reveals generation of an autocrine loop by a mutant epidermal growth factor receptor in glioma cells. Ramnarain, D.B., Park, S., Lee, D.Y., Hatanpaa, K.J., Scoggin, S.O., Otu, H., Libermann, T.A., Raisanen, J.M., Ashfaq, R., Wong, E.T., Wu, J., Elliott, R., Habib, A.A. Cancer Res. (2006) [Pubmed]
  27. The tetraspanin CD9 associates with transmembrane TGF-alpha and regulates TGF-alpha-induced EGF receptor activation and cell proliferation. Shi, W., Fan, H., Shum, L., Derynck, R. J. Cell Biol. (2000) [Pubmed]
  28. Transforming growth factor-alpha induces interleukin-6 in the human keratinocyte cell line HaCaT mainly by transcriptional activation. Aragane, Y., Yamada, H., Schwarz, A., Poppelmann, B., Luger, T.A., Tezuka, T., Schwarz, T. J. Invest. Dermatol. (1996) [Pubmed]
  29. Estrogen receptor alpha mediated induction of the transforming growth factor alpha gene by estradiol and 4-hydroxytamoxifen in MDA-MB-231 breast cancer cells. MacGregor Schafer, J., Liu, H., Levenson, A.S., Horiguchi, J., Chen, Z., Jordan, V.C. J. Steroid Biochem. Mol. Biol. (2001) [Pubmed]
  30. Interactions between stromal cell--derived keratinocyte growth factor and epithelial transforming growth factor in immune-mediated crypt cell hyperplasia. Bajaj-Elliott, M., Poulsom, R., Pender, S.L., Wathen, N.C., MacDonald, T.T. J. Clin. Invest. (1998) [Pubmed]
  31. Tumor necrosis factor alpha-converting enzyme mediates MUC5AC mucin expression in cultured human airway epithelial cells. Shao, M.X., Ueki, I.F., Nadel, J.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  32. Multiple metalloproteinases process protransforming growth factor-alpha (proTGF-alpha). Hinkle, C.L., Mohan, M.J., Lin, P., Yeung, N., Rasmussen, F., Milla, M.E., Moss, M.L. Biochemistry (2003) [Pubmed]
  33. Prevention of apoptosis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the MCF-10A cell line: correlation with increased transforming growth factor alpha production. Davis, J.W., Lauer, F.T., Burdick, A.D., Hudson, L.G., Burchiel, S.W. Cancer Res. (2001) [Pubmed]
  34. Induction of autocrine epidermal growth factor receptor ligands in human keratinocytes by insulin/insulin-like growth factor-1. Vardy, D.A., Kari, C., Lazarus, G.S., Jensen, P.J., Zilberstein, A., Plowman, G.D., Rodeck, U. J. Cell. Physiol. (1995) [Pubmed]
  35. The heparin-binding domain of amphiregulin necessitates the precursor pro-region for growth factor secretion. Thorne, B.A., Plowman, G.D. Mol. Cell. Biol. (1994) [Pubmed]
  36. The binding of HB-EGF to tumour cells is blocked by mAbs which act as EGF and TGF alpha antagonists. Modjtahedi, H., Dean, C. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  37. Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascular endothelial cells. Morimoto, A., Tada, K., Nakayama, Y., Kohno, K., Naito, S., Ono, M., Kuwano, M. Jpn. J. Cancer Res. (1994) [Pubmed]
  38. Involvement of transforming growth factor alpha/epidermal growth factor receptor autocrine growth mechanism in an ovarian cancer cell line in vitro. Morishige, K., Kurachi, H., Amemiya, K., Adachi, H., Inoue, M., Miyake, A., Tanizawa, O., Sakoyama, Y. Cancer Res. (1991) [Pubmed]
  39. Activated extracellular signal-regulated kinases: association with epidermal growth factor receptor/transforming growth factor alpha expression in head and neck squamous carcinoma and inhibition by anti-epidermal growth factor receptor treatments. Albanell, J., Codony-Servat, J., Rojo, F., Del Campo, J.M., Sauleda, S., Anido, J., Raspall, G., Giralt, J., Roselló, J., Nicholson, R.I., Mendelsohn, J., Baselga, J. Cancer Res. (2001) [Pubmed]
  40. Expression and regulation of mRNA coding for acidic and basic fibroblast growth factor and transforming growth factor alpha in cells derived from human skin. Cook, P.W., Coffey, R.J., Magun, B.E., Pittelkow, M.R., Shipley, G.D. Mol. Endocrinol. (1990) [Pubmed]
  41. Epidermal growth factor, epidermal growth factor receptor, and transforming growth factor-alpha in human hyperplastic prostate tissue: expression and cellular localization. De Bellis, A., Ghiandi, P., Comerci, A., Fiorelli, G., Grappone, C., Milani, S., Salerno, R., Marra, F., Serio, M. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  42. Transforming growth factor-alpha-mediated growth pathways in human gastro-intestinal cell lines in relation to the gastrin autocrine pathway. Watson, S.A., Robinson, K.E., McWilliams, D., Michaeli, D., Smith, A.M., Robinson, G. Int. J. Cancer (2000) [Pubmed]
  43. Transforming growth factor alpha and epidermal growth factor levels in bladder cancer and their relationship to epidermal growth factor receptor. Mellon, J.K., Cook, S., Chambers, P., Neal, D.E. Br. J. Cancer (1996) [Pubmed]
  44. Production of transforming growth factor-alpha in human tumour cell lines. Imanishi, K., Yamaguchi, K., Suzuki, M., Honda, S., Yanaihara, N., Abe, K. Br. J. Cancer (1989) [Pubmed]
WikiGenes - Universities