An essential role for ectodomain shedding in mammalian development. Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, Russell WE, Castner BJ, Johnson RS, Fitzner JN, Boyce RW, Nelson N, Kozlosky CJ, Wolfson MF, Rauch CT, Cerretti DP, Paxton RJ, March CJ, Black RA (1998) Science 282: 1281-4 HER2 kinase domain mutation results in constitutive phosphorylation and activation of HER2 and EGFR and resistance to EGFR tyrosine kinase inhibitors. Wang SE, Narasanna A, Perez-Torres M, Xiang B, Wu FY, Yang S, Carpenter G, Gazdar AF, Muthuswamy SK, Arteaga CL (2006) Cancer Cell 10: 25-38 Potentiation of oxyntic atrophy-induced gastric metaplasia in amphiregulin-deficient mice. Nam KT, Varro A, Coffey RJ, Goldenring JR (2007) Gastroenterology 132: 1804-19 Amphiregulin-deficient mice develop spasmolytic polypeptide expressing metaplasia and intestinal metaplasia. Nam KT, Lee HJ, Mok H, Romero-Gallo J, Crowe JE, Peek RM, Goldenring JR (2009) Gastroenterology 136: 1288-96 Epidermal growth factor-related peptides and their relevance to gastrointestinal pathophysiology. Barnard JA, Beauchamp RD, Russell WE, Dubois RN, Coffey RJ (1995) Gastroenterology 108: 564-80 Increased gastroduodenal concentrations of transforming growth factor alpha in adaptation to aspirin in monkeys and rats. Romano M, Lesch CA, Meise KS, Veljaca M, Sanchez B, Kraus ER, Boland CR, Guglietta A, Coffey RJ (1996) Gastroenterology 110: 1448-55 Evidence for repatterning of the gastric fundic epithelium associated with Ménétrier's disease and TGFalpha overexpression. Nomura S, Settle SH, Leys CM, Means AL, Peek RM, Leach SD, Wright CV, Coffey RJ, Goldenring JR (2005) Gastroenterology 128: 1292-305 Increased production of transforming growth factor alpha following acute gastric injury. Polk WH, Dempsey PJ, Russell WE, Brown PI, Beauchamp RD, Barnard JA, Coffey RJ (1992) Gastroenterology 102: 1467-74 Matrix metalloproteinase-7 is expressed by pancreatic cancer precursors and regulates acinar-to-ductal metaplasia in exocrine pancreas. Crawford HC, Scoggins CR, Washington MK, Matrisian LM, Leach SD (2002) J Clin Invest 109: 1437-44 Transforming growth factor alpha protection against drug-induced injury to the rat gastric mucosa in vivo. Romano M, Polk WH, Awad JA, Arteaga CL, Nanney LB, Wargovich MJ, Kraus ER, Boland CR, Coffey RJ (1992) J Clin Invest 90: 2409-21 Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester. DuBois RN, Awad J, Morrow J, Roberts LJ, Bishop PR (1994) J Clin Invest 93: 493-8 Helicobacter pylori upregulates expression of epidermal growth factor-related peptides, but inhibits their proliferative effect in MKN 28 gastric mucosal cells. Romano M, Ricci V, Di Popolo A, Sommi P, Del Vecchio Blanco C, Bruni CB, Ventura U, Cover TL, Blaser MJ, Coffey RJ, Zarrilli R (1998) J Clin Invest 101: 1604-13 HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Covello KL, Kehler J, Yu H, Gordan JD, Arsham AM, Hu CJ, Labosky PA, Simon MC, Keith B (2006) Genes Dev 20: 557-70 Cellular remodeling in heart failure disrupts K(ATP) channel-dependent stress tolerance. Hodgson DM, Zingman LV, Kane GC, Perez-Terzic C, Bienengraeber M, Ozcan C, Gumina RJ, Pucar D, O'Coclain F, Mann DL, Alekseev AE, Terzic A (2003) EMBO J 22: 1732-42 Blockade of the epidermal growth factor receptor tyrosine kinase suppresses tumorigenesis in MMTV/Neu + MMTV/TGF-alpha bigenic mice. Lenferink AE, Simpson JF, Shawver LK, Coffey RJ, Forbes JT, Arteaga CL (2000) Proc Natl Acad Sci U S A 97: 9609-14 Epidermal growth factor receptor activation induces nuclear targeting of cyclooxygenase-2, basolateral release of prostaglandins, and mitogenesis in polarizing colon cancer cells. Coffey RJ, Hawkey CJ, Damstrup L, Graves-Deal R, Daniel VC, Dempsey PJ, Chinery R, Kirkland SC, DuBois RN, Jetton TL, Morrow JD (1997) Proc Natl Acad Sci U S A 94: 657-62 Myristoylated Naked2 escorts transforming growth factor alpha to the basolateral plasma membrane of polarized epithelial cells. Li C, Franklin JL, Graves-Deal R, Jerome WG, Cao Z, Coffey RJ (2004) Proc Natl Acad Sci U S A 101: 5571-6 EGF receptor-independent action of TGF-alpha protects Naked2 from AO7-mediated ubiquitylation and proteasomal degradation. Ding W, Li C, Hu T, Graves-Deal R, Fotia AB, Weissman AM, Coffey RJ (2008) Proc Natl Acad Sci U S A 105: 13433-8 Amphiregulin exosomes increase cancer cell invasion. Higginbotham JN, Demory Beckler M, Gephart JD, Franklin JL, Bogatcheva G, Kremers GJ, Piston DW, Ayers GD, McConnell RE, Tyska MJ, Coffey RJ (2011) Curr Biol 21: 779-86 Acceleration of mammary neoplasia in transforming growth factor alpha transgenic mice by 7,12-dimethylbenzanthracene. Coffey RJ, Meise KS, Matsui Y, Hogan BL, Dempsey PJ, Halter SA (1994) Cancer Res 54: 1678-83 Autonomous growth of androgen-independent human prostatic carcinoma cells: role of transforming growth factor alpha. Hofer DR, Sherwood ER, Bromberg WD, Mendelsohn J, Lee C, Kozlowski JM (1991) Cancer Res 51: 2780-5 Epidermal growth factor receptor (HER1) tyrosine kinase inhibitor ZD1839 (Iressa) inhibits HER2/neu (erbB2)-overexpressing breast cancer cells in vitro and in vivo. Moulder SL, Yakes FM, Muthuswamy SK, Bianco R, Simpson JF, Arteaga CL (2001) Cancer Res 61: 8887-95 Epidermal growth factor receptors in human breast carcinoma cells: a potential selective target for transforming growth factor alpha-Pseudomonas exotoxin 40 fusion protein. Arteaga CL, Hurd SD, Dugger TC, Winnier AR, Robertson JB (1994) Cancer Res 54: 4703-9 Human carcinoid cell production of paracrine growth factors that can stimulate fibroblast and endothelial cell growth. Beauchamp RD, Coffey RJ, Lyons RM, Perkett EA, Townsend CM, Moses HL (1991) Cancer Res 51: 5253-60 Decreased tumor formation in 7,12-dimethylbenzanthracene-treated stromelysin-1 transgenic mice is associated with alterations in mammary epithelial cell apoptosis. Witty JP, Lempka T, Coffey RJ, Matrisian LM (1995) Cancer Res 55: 1401-6 Novel mechanistic insights into ectodomain shedding of EGFR Ligands Amphiregulin and TGF-α: impact on gastrointestinal cancers driven by secondary bile acids. Nagathihalli NS, Beesetty Y, Lee W, Washington MK, Chen X, Lockhart AC, Merchant NB (2014) Cancer Res 74: 2062-72 Inhibition of Epidermal Growth Factor Receptor Activation Is Associated With Improved Diabetic Nephropathy and Insulin Resistance in Type 2 Diabetes. Li Z, Li Y, Overstreet JM, Chung S, Niu A, Fan X, Wang S, Wang Y, Zhang MZ, Harris RC (2018) Diabetes 67: 1847-1857 TACE/ADAM-17: a component of the epidermal growth factor receptor axis and a promising therapeutic target in colorectal cancer. Merchant NB, Voskresensky I, Rogers CM, Lafleur B, Dempsey PJ, Graves-Deal R, Revetta F, Foutch AC, Rothenberg ML, Washington MK, Coffey RJ (2008) Clin Cancer Res 14: 1182-91 Synchronous overexpression of epidermal growth factor receptor and HER2-neu protein is a predictor of poor outcome in patients with stage I non-small cell lung cancer. Onn A, Correa AM, Gilcrease M, Isobe T, Massarelli E, Bucana CD, O'Reilly MS, Hong WK, Fidler IJ, Putnam JB, Herbst RS (2004) Clin Cancer Res 10: 136-43 Treatment with farnesyl-protein transferase inhibitor induces regression of mammary tumors in transforming growth factor (TGF) alpha and TGF alpha/neu transgenic mice by inhibition of mitogenic activity and induction of apoptosis. Nørgaard P, Law B, Joseph H, Page DL, Shyr Y, Mays D, Pietenpol JA, Kohl NE, Oliff A, Coffey RJ, Poulsen HS, Moses HL (1999) Clin Cancer Res 5: 35-42 Loss of TGF-beta type II receptor in fibroblasts promotes mammary carcinoma growth and invasion through upregulation of TGF-alpha-, MSP- and HGF-mediated signaling networks. Cheng N, Bhowmick NA, Chytil A, Gorksa AE, Brown KA, Muraoka R, Arteaga CL, Neilson EG, Hayward SW, Moses HL (2005) Oncogene 24: 5053-68 Use of fluorescence-activated vesicle sorting for isolation of Naked2-associated, basolaterally targeted exocytic vesicles for proteomics analysis. Cao Z, Li C, Higginbotham JN, Franklin JL, Tabb DL, Graves-Deal R, Hill S, Cheek K, Jerome WG, Lapierre LA, Goldenring JR, Ham AJ, Coffey RJ (2008) Mol Cell Proteomics 7: 1651-67 Pancreatic epithelial plasticity mediated by acinar cell transdifferentiation and generation of nestin-positive intermediates. Means AL, Meszoely IM, Suzuki K, Miyamoto Y, Rustgi AK, Coffey RJ, Wright CV, Stoffers DA, Leach SD (2005) Development 132: 3767-76 From wavy hair to naked proteins: the role of transforming growth factor alpha in health and disease. Singh B, Coffey RJ (2014) Semin Cell Dev Biol 28: 12-21 Altered TGF-α/β signaling drives cooperation between breast cancer cell populations. Franco OE, Tyson DR, Konvinse KC, Udyavar AR, Estrada L, Quaranta V, Crawford SE, Hayward SW (2016) FASEB J 30: 3441-3452 MiR-374a suppresses lung adenocarcinoma cell proliferation and invasion by targeting TGFA gene expression. Wu H, Liu Y, Shu XO, Cai Q (2016) Carcinogenesis 37: 567-75 Mitogenic activity and signaling mechanism of 2-(14,15- epoxyeicosatrienoyl)glycerol, a novel cytochrome p450 arachidonate metabolite. Chen J, Chen JK, Falck JR, Guthi JS, Anjaiah S, Capdevila JH, Harris RC (2007) Mol Cell Biol 27: 3023-34 Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab. Wang SE, Xiang B, Guix M, Olivares MG, Parker J, Chung CH, Pandiella A, Arteaga CL (2008) Mol Cell Biol 28: 5605-20 Potential physiologic roles for epidermal growth factor in the kidney. Harris RC (1991) Am J Kidney Dis 17: 627-30 Amphiregulin acts as an autocrine growth factor in two human polarizing colon cancer lines that exhibit domain selective EGF receptor mitogenesis. Damstrup L, Kuwada SK, Dempsey PJ, Brown CL, Hawkey CJ, Poulsen HS, Wiley HS, Coffey RJ (1999) Br J Cancer 80: 1012-9
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