In order to fulfill its function of producing and delivering sufficient milk to newborn mammalian offspring, the mammary gland first has to form an extensive ductal network. As in all phases of mammary development, hormonal cues elicit local intra- and inter-cellular signaling cascades that regulate ductal growth and differentiation. Among other things, ductal development requires the epidermal growth factor receptor (EGFR), its ligand amphiregulin (AREG), and the transmembrane metalloproteinase ADAM17, which can cleave and release AREG from the cell surface so that it may interact with its receptor. Tissue recombination and transplantation studies demonstrate that EGFR phosphorylation and ductal development proceed only when ADAM17 and AREG are expressed on mammary epithelial cells and EGFR is present on stromal cells, and that local administration of soluble AREG can rescue the development of ADAM17-deficient transplants. Thus proper mammary morphogenesis requires the ADAM17-mediated release of AREG from ductal epithelial cells, the subsequent activation of EGFR on stromal cells, and EGFR-dependent stromal responses that in return elicit a new set of epithelial responses, all culminating in the formation of a fully functional ductal tree. This, however, raises new issues concerning what may act upstream, downstream or in parallel with the ADAM17–AREG–EGFR axis, how it may become hijacked or corrupted during the onset and evolution of cancer, and how such ill effects may be confronted.
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a disintegrin and metalloproteinase
epidermal growth factor
epidermal growth factor receptor
extracellular matrix metalloproteinase inducer
extracellular signal-regulated kinase
fibroblast growth factor
fibroblast growth factor receptor
G-protein coupled receptor
heparin-binding EGF-like growth factor
insulin-like growth factor
mitogen-activated protein kinase
tumor necrosis factor alpha converting enzyme
terminal end bud
transforming growth factor
tissue inhibitor of metalloproteinases
Sternlicht MD. Key stages in mammary gland development: the cues that regulate ductal branching morphogenesis. Breast Cancer Res. 2006;8:201.
Sternlicht MD, Kouros-Mehr H, Lu P, Werb Z. Hormonal and local control of mammary branching morphogenesis. Differentiation 2006;74:365–81.
Affolter M, Bellusci S, Itoh N, Shilo B, Thiery JP, Werb Z. Tube or not tube: remodeling epithelial tissues by branching morphogenesis. Dev Cell. 2003;4:11–8.
Davies JA. Do different branching epithelia use a conserved developmental mechanism? Bioessays 2002;24:937–48.
Hens JR, Wysolmerski JJ. Key stages of mammary gland development: molecular mechanisms involved in the formation of the embryonic mammary gland. Breast Cancer Res. 2005;7:220–4.
Hinck L, Silberstein GB. Key stages of mammary gland development: the mammary end bud as a motile organ. Breast Cancer Res. 2005;7:245–51.
Oakes SR, Hilton HN, Ormandy CJ. The alveolar switch: coordinating the proliferative cues and cell fate decisions that drive the formation of lobuloalveoli from ductal epithelium. Breast Cancer Res. 2006;8:207.
Curtis Hewitt S, Couse JF, Korach KS. Estrogen receptor transcription and transactivation: estrogen receptor knockout mice: what their phenotypes reveal about mechanisms of estrogen action. Breast Cancer Res. 2000;2:345–52.
Bocchinfuso WP, Lindzey JK, Hewitt SC, Clark JA, Myers PH, Cooper R, et al. Induction of mammary gland development in estrogen receptor-alpha knockout mice. Endocrinology 2000;141:2982–94.
Sakakura T, Nishizuka Y, Dawe CJ. Mesenchyme-dependent morphogenesis and epithelium-specific cytodifferentiation in mouse mammary gland. Science 1976;194:1439–41.
Kusakabe M, Sakakura T, Sano M, Nishizuka Y. A pituitary–salivary mixed gland induced by tissue recombination of embryonic pituitary epithelium and embryonic submandibular gland mesenchyme in mice. Dev Biol. 1985;110:382–91.
Cunha GR, Young P, Christov K, Guzman R, Nandi S, Talamantes F, et al. Mammary phenotypic expression induced in epidermal cells by embryonic mammary mesenchyme. Acta Anat (Basel). 1995;152:195–204.
Propper A, Gomot L. Control of chick epidermis differentiation by rabbit mammary mesenchyme. Experientia 1973;29:1543–4.
Naylor MJ, Ormandy CJ. Mouse strain-specific patterns of mammary epithelial ductal side branching are elicited by stromal factors. Dev Dyn. 2002;225:100–5.
Kuperwasser C, Chavarria T, Wu M, Magrane G, Gray JW, Carey L, et al. Reconstruction of functionally normal and malignant human breast tissues in mice. Proc Natl Acad Sci U S A. 2004;101:4966–71.
Parmar H, Young P, Emerman JT, Neve RM, Dairkee S, Cunha GR. A novel method for growing human breast epithelium in vivo using mouse and human mammary fibroblasts. Endocrinology 2002;143:4886–96.
Harris RC, Chung E, Coffey RJ. EGF receptor ligands. Exp Cell Res. 2003;284:2–13.
Turkington RW. The role of epithelial growth factor in mammary gland development in vitro. Exp Cell Res. 1969;57:79–85.
Tonelli QJ, Sorof S. Epidermal growth factor requirement for development of cultured mammary gland. Nature 1980;285:250–2.
Richards J, Guzman R, Konrad M, Yang J, Nandi S. Growth of mouse mammary gland end buds cultured in a collagen gel matrix. Exp Cell Res. 1982;141:433–43.
Fowler KJ, Walker F, Alexander W, Hibbs ML, Nice EC, Bohmer RM, et al. A mutation in the epidermal growth factor receptor in waved-2 mice has a profound effect on receptor biochemistry that results in impaired lactation. Proc Natl Acad Sci U S A. 1995;92:1465–9.
Sebastian J, Richards RG, Walker MP, Wiesen JF, Werb Z, Derynck R, et al. Activation and function of the epidermal growth factor receptor and erbB-2 during mammary gland morphogenesis. Cell Growth Differ. 1998;9:777–85.
Xie W, Paterson AJ, Chin E, Nabell LM, Kudlow JE. Targeted expression of a dominant negative epidermal growth factor receptor in the mammary gland of transgenic mice inhibits pubertal mammary duct development. Mol Endocrinol. 1997;11:1766–81.
Schroeder JA, Lee DC. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ. 1998;9:451–64.
Luetteke NC, Qiu TH, Fenton SE, Troyer KL, Riedel RF, Chang A, et al. Targeted inactivation of the EGF and amphiregulin genes reveals distinct roles for EGF receptor ligands in mouse mammary gland development. Development 1999;126:2739–50.
Coleman S, Silberstein GB, Daniel CW. Ductal morphogenesis in the mouse mammary gland: evidence supporting a role for epidermal growth factor. Dev Biol. 1988;127:304–15.
Wiesen JF, Young P, Werb Z, Cunha GR. Signaling through the stromal epidermal growth factor receptor is necessary for mammary ductal development. Development 1999;126:335–44.
Sternlicht MD, Sunnarborg SW, Kouros-Mehr H, Yu Y, Lee DC, Werb Z. Mammary ductal morphogenesis requires paracrine activation of stromal EGFR via ADAM17-dependent shedding of epithelial amphiregulin. Development 2005;132:3923–33.
D'Cruz CM, Moody SE, Master SR, Hartman JL, Keiper EA, Imielinski MB, et al. Persistent parity-induced changes in growth factors, TGF-beta3, and differentiation in the rodent mammary gland. Mol Endocrinol. 2002;16:2034–51.
Jackson LF, Qiu TH, Sunnarborg SW, Chang A, Zhang C, Patterson C, et al. Defective valvulogenesis in HB-EGF and TACE-null mice is associated with aberrant BMP signaling. Embo J. 2003;22:2704–16.
Kenney NJ, Smith GH, Rosenberg K, Cutler ML, Dickson RB. Induction of ductal morphogenesis and lobular hyperplasia by amphiregulin in the mouse mammary gland. Cell Growth Differ. 1996;7:1769–81.
Kenney NJ, Bowman A, Korach KS, Barrett JC, Salomon DS. Effect of exogenous epidermal-like growth factors on mammary gland development and differentiation in the estrogen receptor-alpha knockout (ERKO) mouse. Breast Cancer Res Treat. 2003;79:161–73.
Snedeker SM, Brown CF, DiAugustine RP. Expression and functional properties of transforming growth factor alpha and epidermal growth factor during mouse mammary gland ductal morphogenesis. Proc Natl Acad Sci U S A. 1991;88:276–80.
Hinkle CL, Sunnarborg SW, Loiselle D, Parker CE, Stevenson M, Russell WE, et al. Selective roles for tumor necrosis factor alpha-converting enzyme/ADAM17 in the shedding of the epidermal growth factor receptor ligand family: the juxtamembrane stalk determines cleavage efficiency. J Biol Chem. 2004;279:24179–88.
Sunnarborg SW, Hinkle CL, Stevenson M, Russell WE, Raska CS, Peschon JJ, et al. Tumor necrosis factor-alpha converting enzyme (TACE) regulates epidermal growth factor receptor ligand availability. J Biol Chem. 2002;277:12838–45.
Sahin U, Weskamp G, Kelly K, Zhou HM, Higashiyama S, Peschon J, et al. Distinct roles for ADAM10 and ADAM17 in ectodomain shedding of six EGFR ligands. J Cell Biol. 2004;164:769–79.
Blobel CP. ADAMs: key components in EGFR signalling and development. Nat Rev Mol Cell Biol. 2005;6:32–43.
Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J. TACE is required for the activation of the EGFR by TGF-alpha in tumors. Embo J. 2003;22:1114–24.
Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, et al. An essential role for ectodomain shedding in mammalian development. Science 1998;282:1281–4.
Shi W, Chen H, Sun J, Buckley S, Zhao J, Anderson KD, et al. TACE is required for fetal murine cardiac development and modeling. Dev Biol. 2003;261:371–80.
Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC. TGF alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell 1993;73:263–78.
Mann GB, Fowler KJ, Gabriel A, Nice EC, Williams RL, Dunn AR. Mice with a null mutation of the TGF alpha gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 1993;73:249–61.
Iwamoto R, Yamazaki S, Asakura M, Takashima S, Hasuwa H, Miyado K, et al. Heparin-binding EGF-like growth factor and ErbB signaling is essential for heart function. Proc Natl Acad Sci U S A. 2003;100:3221–6.
Yamazaki S, Iwamoto R, Saeki K, Asakura M, Takashima S, Yamazaki A, et al. Mice with defects in HB-EGF ectodomain shedding show severe developmental abnormalities. J Cell Biol. 2003;163:469–75.
Miettinen PJ, Berger JE, Meneses J, Phung Y, Pedersen RA, Werb Z, et al. Epithelial immaturity and multiorgan failure in mice lacking epidermal growth factor receptor. Nature 1995;376:337–41.
Sibilia M, Wagner EF. Strain-dependent epithelial defects in mice lacking the EGF receptor. Science 1995;269:234–8.
Threadgill DW, Dlugosz AA, Hansen LA, Tennenbaum T, Lichti U, Yee D, et al. Targeted disruption of mouse EGF receptor: effect of genetic background on mutant phenotype. Science 1995;269:230–4.
Lee MH, Rapti M, Murphy G. Delineating the molecular basis of the inactivity of tissue inhibitor of metalloproteinase-2 against tumor necrosis factor-alpha-converting enzyme. J Biol Chem. 2004;279:45121–9.
Schuger L, Johnson GR, Gilbride K, Plowman GD, Mandel R. Amphiregulin in lung branching morphogenesis: interaction with heparan sulfate proteoglycan modulates cell proliferation. Development 1996;122:1759–67.
Varela LM, Darcy KM, Ip MM. The epidermal growth factor receptor is not required for tumor necrosis factor-alpha action in normal mammary epithelial cells. Endocrinology 1997;138:3891–900.
Lee PP, Hwang JJ, Murphy G, Ip MM. Functional significance of MMP-9 in tumor necrosis factor-induced proliferation and branching morphogenesis of mammary epithelial cells. Endocrinology 2000;141:3764–73.
Pasparakis M, Alexopoulou L, Episkopou V, Kollias G. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response. J Exp Med. 1996;184:1397–411.
Marino MW, Dunn A, Grail D, Inglese M, Noguchi Y, Richards E, et al. Characterization of tumor necrosis factor-deficient mice. Proc Natl Acad Sci U S A. 1997;94:8093–8.
Peschon JJ, Torrance DS, Stocking KL, Glaccum MB, Otten C, Willis CR, et al. TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol. 1998;160:943–52.
Daniel CW, Silberstein GB, Strickland P. Direct action of 17 beta-estradiol on mouse mammary ducts analyzed by sustained release implants and steroid autoradiography. Cancer Res. 1987;47:6052–7.
Kleinberg DL, Feldman M, Ruan W. IGF-I: an essential factor in terminal end bud formation and ductal morphogenesis. J Mammary Gland Biol Neoplasia. 2000;5:7–17.
Gallego MI, Binart N, Robinson GW, Okagaki R, Coschigano KT, Perry J, et al. Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Dev Biol. 2001;229:163–75.
Fisher CR, Graves KH, Parlow AF, Simpson ER. Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci U S A. 1998;95:6965–70.
Bonnette SG, Hadsell DL. Targeted disruption of the IGF-I receptor gene decreases cellular proliferation in mammary terminal end buds. Endocrinology 2001;142:4937–45.
Cunha GR, Young P, Hom YK, Cooke PS, Taylor JA, Lubahn DB. Elucidation of a role for stromal steroid hormone receptors in mammary gland growth and development using tissue recombinants. J Mammary Gland Biol Neoplasia. 1997;2:393–402.
Mueller SO, Clark JA, Myers PH, Korach KS. Mammary gland development in adult mice requires epithelial and stromal estrogen receptor alpha. Endocrinology 2002;143:2357–65.
Mallepell S, Krust A, Chambon P, Brisken C. Paracrine signaling through the epithelial estrogen receptor alpha is required for proliferation and morphogenesis in the mammary gland. Proc Natl Acad Sci U S A. 2006;103:2196–201.
Vendrell JA, Magnino F, Danis E, Duchesne MJ, Pinloche S, Pons M, et al. Estrogen regulation in human breast cancer cells of new downstream gene targets involved in estrogen metabolism, cell proliferation and cell transformation. J Mol Endocrinol. 2004;32:397–414.
Schafer B, Gschwind A, Ullrich A. Multiple G-protein-coupled receptor signals converge on the epidermal growth factor receptor to promote migration and invasion. Oncogene 2004;23:991–9.
Srour N, Lebel A, McMahon S, Fournier I, Fugere M, Day R, et al. TACE/ADAM-17 maturation and activation of sheddase activity require proprotein convertase activity. FEBS Lett. 2003;554:275–83.
Horiuchi K, Le Gall S, Schulte M, Yamaguchi T, Reiss K, Murphy G, et al. Substrate selectivity of epidermal growth factor-receptor ligand sheddases and their regulation by phorbol esters and calcium influx. Mol Biol Cell. 2007;18:176–88.
Lemjabbar H, Li D, Gallup M, Sidhu S, Drori E, Basbaum C. Tobacco smoke-induced lung cell proliferation mediated by tumor necrosis factor alpha-converting enzyme and amphiregulin. J Biol Chem. 2003;278:26202–7.
Gschwind A, Hart S, Fischer OM, Ullrich A. TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells. Embo J. 2003;22:2411–21.
Ohtsu H, Dempsey PJ, Eguchi S. ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am J Physiol Cell Physiol. 2006;291:C1–10.
Diaz-Rodriguez E, Montero JC, Esparis-Ogando A, Yuste L, Pandiella A. Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding. Mol Biol Cell. 2002;13:2031–44.
Fan H, Turck CW, Derynck R. Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-alpha converting enzyme and of an alternatively translated polypeptide. J Biol Chem. 2003;278:18617–27.
Reddy P, Slack JL, Davis R, Cerretti DP, Kozlosky CJ, Blanton RA, et al. Functional analysis of the domain structure of tumor necrosis factor-alpha converting enzyme. J Biol Chem. 2000;275:14608–14.
Bax DV, Messent AJ, Tart J, van Hoang M, Kott J, Maciewicz RA, et al. Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells. J Biol Chem. 2004;279:22377–86.
Tanaka M, Nanba D, Mori S, Shiba F, Ishiguro H, Yoshino K, et al. ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands. J Biol Chem. 2004;279:41950–9.
Santiago-Josefat B, Esselens C, Bech-Serra JJ, Arribas J. Post-transcriptional up-regulation of ADAM17 upon epidermal growth factor receptor activation and in breast tumors. J Biol Chem. 2007;282:8325–31.
Jones FE, Stern DF. Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation. Oncogene 1999;18:3481–90.
Jackson-Fisher AJ, Bellinger G, Ramabhadran R, Morris JK, Lee KF, Stern DF. ErbB2 is required for ductal morphogenesis of the mammary gland. Proc Natl Acad Sci U S A. 2004;101:17138–43.
Andrechek ER, White D, Muller WJ. Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth. Oncogene 2005;24:932–7.
Tidcombe H, Jackson-Fisher A, Mathers K, Stern DF, Gassmann M, Golding JP. Neural and mammary gland defects in ErbB4 knockout mice genetically rescued from embryonic lethality. Proc Natl Acad Sci U S A. 2003;100:8281–6.
Simian M, Hirai Y, Navre M, Werb Z, Lochter A, Bissell MJ. The interplay of matrix metalloproteinases, morphogens and growth factors is necessary for branching of mammary epithelial cells. Development 2001;128:3117–31.
Jones FE, Welte T, Fu XY, Stern DF. ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J Cell Biol. 1999;147:77–88.
Li L, Cleary S, Mandarano MA, Long W, Birchmeier C, Jones FE. The breast proto-oncogene, HRGalpha regulates epithelial proliferation and lobuloalveolar development in the mouse mammary gland. Oncogene 2002;21:4900–7.
Jones JT, Akita RW, Sliwkowski MX. Binding specificities and affinities of egf domains for ErbB receptors. FEBS Lett. 1999;447:227–31.
Fata JE, Leco KJ, Moorehead RA, Martin DC, Khokha R. Timp-1 is important for epithelial proliferation and branching morphogenesis during mouse mammary development. Dev Biol. 1999;211:238–54.
Wiseman BS, Sternlicht MD, Lund LR, Alexander CM, Mott J, Bissell MJ, et al. Site-specific inductive and inhibitory activities of MMP-2 and MMP-3 orchestrate mammary gland branching morphogenesis. J Cell Biol. 2003;162:1123–33.
Menashi S, Serova M, Ma L, Vignot S, Mourah S, Calvo F. Regulation of extracellular matrix metalloproteinase inducer and matrix metalloproteinase expression by amphiregulin in transformed human breast epithelial cells. Cancer Res. 2003;63:7575–80.
Kheradmand F, Rishi K, Werb Z. Signaling through the EGF receptor controls lung morphogenesis in part by regulating MT1-MMP-mediated activation of gelatinase A/MMP2. J Cell Sci. 2002;115:839–48.
Lu P, Ewald A, Martin G, Werb Z. Essential function of FGF signaling pathway during branching morphogenesis of mammary gland (abstract #515). Dev Biol. 2005;283:680–1.
Steinberg Z, Myers C, Heim VM, Lathrop CA, Rebustini IT, Stewart JS, et al. FGFR2b signaling regulates ex vivo submandibular gland epithelial cell proliferation and branching morphogenesis. Development 2005;132:1223–34.
Entesarian M, Matsson H, Klar J, Bergendal B, Olson L, Arakaki R, et al. Mutations in the gene encoding fibroblast growth factor 10 are associated with aplasia of lacrimal and salivary glands. Nat Genet. 2005;37:125–8.
Weaver M, Dunn NR, Hogan BL. Bmp4 and Fgf10 play opposing roles during lung bud morphogenesis. Development 2000;127:2695–704.
Tang MJ, Cai Y, Tsai SJ, Wang YK, Dressler GR. Ureteric bud outgrowth in response to RET activation is mediated by phosphatidylinositol 3-kinase. Dev Biol. 2002;243:128–36.
Watanabe T, Costantini F. Real-time analysis of ureteric bud branching morphogenesis in vitro. Dev Biol. 2004;271:98–108.
Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y. Clinical relevance of amphiregulin and VEGF in primary breast cancers. Int J Cancer. 2004;111:733–40.
Lendeckel U, Kohl J, Arndt M, Carl-McGrath S, Donat H, Rocken C. Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol. 2005;131:41–8.
Umekita Y, Ohi Y, Sagara Y, Yoshida H. Co-expression of epidermal growth factor receptor and transforming growth factor-alpha predicts worse prognosis in breast-cancer patients. Int J Cancer. 2000;89:484–7.
Ma L, de Roquancourt A, Bertheau P, Chevret S, Millot G, Sastre-Garau X, et al. Expression of amphiregulin and epidermal growth factor receptor in human breast cancer: analysis of autocriny and stromal–epithelial interactions. J Pathol. 2001;194:413–9.
LeJeune S, Leek R, Horak E, Plowman G, Greenall M, Harris AL. Amphiregulin, epidermal growth factor receptor, and estrogen receptor expression in human primary breast cancer. Cancer Res. 1993;53:3597–602.
Niemeyer CC, Spencer-Dene B, Wu JX, Adamson ED. Preneoplastic mammary tumor markers: Cripto and Amphiregulin are overexpressed in hyperplastic stages of tumor progression in transgenic mice. Int J Cancer. 1999;81:588–91.
Ma L, Gauville C, Berthois Y, Millot G, Johnson GR, Calvo F. Antisense expression for amphiregulin suppresses tumorigenicity of a transformed human breast epithelial cell line. Oncogene 1999;18:6513–20.
Brandt R, Eisenbrandt R, Leenders F, Zschiesche W, Binas B, Juergensen C, et al. Mammary gland specific hEGF receptor transgene expression induces neoplasia and inhibits differentiation. Oncogene 2000;19:2129–37.
Kenny PA, Bissell MJ. Targeting TACE-dependent EGFR ligand shedding in breast cancer. J Clin Invest. 2007;117:337–45.
We thank Drs. Zena Werb and David Lee for their guidance and support. This work was supported by grants from the National Cancer Institute (CA57621, CA58207, CA43793, CA61896 and CA85410) and by a grant jointly funded by the National Institute of Environmental Health Sciences and National Cancer Institute (ES012801).
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Sternlicht, M.D., Sunnarborg, S.W. The ADAM17–amphiregulin–EGFR Axis in Mammary Development and Cancer. J Mammary Gland Biol Neoplasia 13, 181–194 (2008). https://doi.org/10.1007/s10911-008-9084-6
- Mammary gland
- Branching morphogenesis
- TNFα converting enzyme
- Stromal–epithelial interactions
- Epidermal growth factor receptor