Summary
A number of different epidermal growth factor (EGF)-related peptides such as EGF, transforming growth factor α (TGFα), amphiregulin (AR), heregulin (HRG), and cripto-1 (CR-1), are coexpressed to varying degrees in both normal and malignant mammary epithelial cells. However, in general the frequency and level of expression of TGFα, AR, and CR-1 are higher in malignant breast epithelial cells than in normal mammary epithelium. In addition, several of these peptides such as TGFα and AR can function as autocrine and/or juxtacrine growth factors in mammary epithelial cells, and their expression is stringently regulated by mammotrophic hormones such as estrogens, activated proto-oncogenes that have been implicated in the pathogenesis of breast cancer, and other growth factors. The redundancy of expression that is observed for a number of these structurally related peptides in both normal and malignant mammary epithelial cells suggests that some of these peptides may be involved in regulating other aspects of cellular behavior such as differentiation in addition to proliferation.
References
Goustin AS, Leof AB, Shipley GD: Growth factors and cancer. Cancer Res 46:1015–1029, 1986
Salomon DS, Dickson RB, Normanno N, Saeki T, Kim N, Kenney N, Ciardiello F: Interaction of oncogenes and growth factors in colon and breast cancer.In: Spandidos DA (ed) Current Perspectives on Molecular and Cellular Oncology. JAI Press Ltd., London, 1992, pp 211–261
Aaronson SA: Growth factors and cancer. Science 254:1146–1153, 1991
Sporn MB, Roberts A: Autocrine secretion — ten years later. Ann Intern Med 117:408–414, 1992
Salomon DS, Kim N, Saeki T, Ciardiello F: Transforming growth factor-α: an oncodevelopmental growth factor. Cancer Cells 2:389–397, 1990
Ciardiello F, McGeady ML, Kim N, Basolo F, Hynes NE, Langton B, Yokozaki H, Saeki T, Elliott J, Masui H, Mendelsohn J, Soule H, Russo J, Salomon DS: Transforming growth factor-α expression is enhanced in human mammary epithelial cells transformed by an activated c-Ha-ras protooncogene but not by the c-neu protooncogene, and overexpression of the transforming growth factor-α complementary DNA leads to transformation. Cell Growth Diff 1:407–420, 1990
Ciardiello F, Dono R, Kim N, Persico MG, Salomon DS: Expression of cripto, a novel gene of the epidermal growth factor gene family, leads to in vitro transformation of a normal mouse mammary epithelial cell line. Cancer Res 51:1051–1054, 1991
Ciccodicola A, Dono R, Obici S, Simeone A, Zollo M, Persico MG: Molecular characterization of a gene of the EGF family expressed in undifferentiated human NTERA-2 teratocarcinoma cells. EMBO J 8:1987–1991, 1989
Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, Yansura D, Abadi N, Raab H, Lewis GD, Shepard MH, Kuang WJ, Wood WI, Goeddel DV, Vandlen RL: Identification of Heregulin, a specific activator of p185erbB-2. Science 256:1205–1210, 1992
Plowman GD, Culouscou J-M, Whitney GS, Green JM, Carlton GW, Foy L, Neubauer MG, Shoyab M: Ligand-specific activation of HER4/p180erbB-4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci USA 90:1746–1750, 1993
Kraus MH, Issing W, Miki T, Popescu N, Aaronson S: Isolation and characterization oferbB-3, a third member of theerbB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci USA 86:9193–9197, 1989
Derynck R: Transforming growth factor alpha. Cell 54:593–595, 1988
Todaro GJ, Rose TM, Spooner CE, Shoyab M, Plowman GD: Cellular and viral ligands that interact with the EGF receptor. Semin Cancer Biol 1:257–263, 1990
Massagué J: Transforming growth factor α. J Biol Chem 256:21393–21396, 1993
Jakowlew SB, Kondaiah P, Flanders KC, Thompson NL, Dillard PJ, Sporn MB, Roberts AB: Increased expression of growth factor mRNAs accompanies viral transformation of rodent cells. Onc Res 2:135–148, 1988
Ciardiello F, Valverius EM, Colucci-D'Amato GL, Kim N, Bassin RH, Salomon DS: Differential growth factor expression in transformed mouse NIH-3T3 cells. J Cell Biochem 42:45–57, 1990
Valverius EM, Bates SE, Stampfer M, Clark R, McCormick F, Salomon DS, Lippman ME, Dickson RB: Transforming growth factor alpha production and epidermal growth factor receptor expression in normal and oncogene transformed human mammary epithelial cells. Mol Endocrinol 3:203–214, 1989
Bates SE, Valverius EM, Ennis BW, Bronzert DA, Sheridan JP, Stampfer M, Mendelsohn J, Lippman ME, Dickson RB: Expression of the TGF-alpha/EGF receptor pathway in normal human breast epithelial cells. Endocrinol 126:596–607, 1990
Vondherhaar B: Local effect of EGF, α-TGF and EGF-like growth factors on lobuloalveolar development of the mouse mammary glandin vivo. J Cell Physiol 132:581–584, 1987
Ciardiello F, Hynes NE, Kim N, Valverius EM, Lippman ME, Salomon DS: Transformation of mouse mammary epithelial cells with the Ha-ras but not with the neu oncogene results in a gene dosage-dependent increase in transforming growth factor-alpha production. FEBS Lett 250:474–478, 1989
Ciardiello F, Kim N, Hynes NE, Jaggi R, Redmond SMS, Liscia DS, Sanfilippo B, Merlo G, Callahan R, Kidwell W, Salomon DS: Induction of transforming growth factor α expression in mouse mammary epithelial cells after transformation with a point mutated c-Ha-ras protooncogene. Mol Endocrinol 2:1202–1216, 1988
Liu SC, Sanfilippo B, Perroteau I, Derynck R, Salomon DS, Kidwell WR: Expression of transforming growth factor α (TGFα) in differentiated rat mammary tumors: estrogen induction of TGFα production. Mol Endocrinol 1:683–692, 1987
Manni A, Wright C, Badger B, Bartholomew M, Herlyn M, Mendelsohn J, Masui H, Demers L: Role of transforming growth factor α related peptides in the autocrine/paracrine control of experimental breast cancer growthin vitro by estradiol, prolactin, and progesterone. Breast Cancer Res Treat 15:73–83, 1990
Salomon DS, Zwiebel JA, Bano M, Losonczy I, Fehnel P, Kidwell WR: Presence of transforming growth factors in human breast cancer cells. Cancer Res 44:4069–4077, 1984
Perroteau I, Salomon DS, Debortoli M, Kidwell W, Hazarika P, Pardue R, Dedman J, Tam J: Immunological detection and quantitation of alpha transforming growth factors in human breast carcinoma cells. Breast Cancer Res Treat 7:201–210, 1986
Bates SE, Davidson N, Valverius EM, Freter C, Dickson RB, Tam J, Kudlow J, Lippman ME, Salomon DS: Expression of transforming growth factor α and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance. Mol Endocrinol 2:543–555, 1988
Murphy LC and Dotzlaw H: Regulation of transforming growth factor α and transforming growth factor β messenger ribonucleic acid abundance in T-47D human breast cancer cells. Mol Endocrinol 3:611–616, 1989
Saeki T, Cristiano A, Lynch MJ, Brattain M, Kim N, Normanno N, Kenney N, Ciardiello F, Salomon DS: Regulation by estrogen through the 5'-flanking region of the transforming growth factor alpha gene. Mol Endocrinol 5:1955–1963, 1991
Noguchi S, Motomura K, Inaji H, Imaoka S, Koyama H: Down-regulation of transforming growth factor-α by tamoxifen in human breast cancer. Cancer 72:131–136, 1993
Gregory H, Thomas CE, Willshire TR, Young JA, Andersson H, Baildam A, Howell A: Epidermal growth factor and transforming growth factor α in patients with breast tumors. Br J Cancer 59:605–609, 1989
Kenney N, Saeki T, Gottardis M, Kim N, Garcia-Morales P, Martin MB, Normanno N, Ciardiello F, Day A, Cutler ML, Salomon DS: Expression of transforming growth factor α (TGFα) antisense mRNA inhibits the estrogen-induced production of TGFα and estrogen-induced proliferation of estrogen-responsive human breast cancer cells. J Cell Physiol 156:497–514, 1993
Hynes NE, Taverna D, Harwerth IM, Ciardiello F, Salomon DS, Yamamoto T, Groner B: Epidermal growth factor receptor, but not c-erbB-2, activation prevents lactogenic hormone induction of the betacasein gene in mouse mammary epithelial cells. Mol Cell Biol 10:4027–4034, 1990
Rosenthal A, Lindquist PB, Bringman TS, Goeddel DV, Derynck R: Expression in rat fibroblasts of a human transforming growth factor-α cDNA results in transformation. Cell 46:301–309, 1986
Di Marco E, Pierce JH, Fleming TP, Kraus MH, Molloy CJ, Aaronson SA, Di Fiore PP: Autocrine interaction between TGFα and the EGF-receptor: quantitative requirements for induction of the malignant phenotype. Oncogene 4:831–838, 1989
Shankar V, Ciardiello F, Kim N, Derynck R, Liscia DS, Merlo G, Langton B, Sheer D, Callahan R, Bassin R, Lippman R, Hynes NE, Salomon DS: Transformation of an established mouse mammary epithelial cell line following transfection with a human transforming growth factor alpha cDNA. Mol Carcin 2:1–11, 1989
McGeady ML, Kerby S, Shankar V, Ciardiello F, Salomon DS, Seidman M: Infection with a TGFα retroviral vector transforms normal mouse mammary epithelial cells but not normal fibroblasts. Oncogene 4:1375–1382, 1989
Sandgren EP, Luetteke NC, Palmiter R, Brinster R, Lee DC: Overexpression of TGFα in transgenic mice: induction of epithelial hyperplasia, pancreatic metaplasia and carcinoma of the breast. Cell 61:1121–1135, 1990
Jhappan C, Stahle C, Harkins R, Fausto N, Smith G, Merlino GT: TGFα overexpression in transgenic mice induces liver neoplasia and abnormal development of the mammary gland and pancreas. Cell 61:1137–1146, 1990
Matsui Y, Halter S, Holt JT, Hogan BLM, Coffey RJ: Development of mammary hyperplasia and neoplasia in MMTV-TGFα transgenic mice. Cell 61:1137–1146, 1990
Travers MT, Barrett-Lee PJ, Berger U, Lugmani YA, Gazet JC, Powels TJ, Coombes CR: Growth factor expression in normal, benign and malignant breast tissue. Br Med J 296:1621–1625, 1988
Ciardiello F, Kim N, Liscia DS, Bianco C, Lidereau R, Merlo G, Callahan R, Greiner J, Szpak C, Kidwell W, Schlom J, Salomon DS: Transforming growth factor α (TGFα) mRNA expression in human breast carcinomas and TGFα activity in the effusions of breast cancer patients. J Natl Cancer Inst 81:1165–1171, 1989
Murray PA, Barrett-Lee PJ, Travers MT, Lugmani Y, Powles T, Coombes RC: The prognostic significance of transforming growth factors in breast cancer. Br J Cancer 67:1408–1412, 1993
Dublin EA, Barnes DM, Wang DY, King RJB, Levison DA: TGF alpha and TGF beta expression in mammary carcinoma. J Pathol 170:15–22, 1993
Barrett-Lee PJ, Travers MT, Lugmani Y, Coombes RC: Transcripts for transforming growth factors in human breast cancer: clinical correlates. Br J Cancer 61:612–617, 1990
Parkam DH, Jankowski J: Transforming growth factor α in epithelial proliferative diseases of the breast. J Clin Pathol 45:513–516, 1992
Macias A, Perez R, Hagerstrom T, Skoog L: Transforming growth factor α in human mammary carcinomas and their metastases. Anticancer Res 9:177–182, 1989
Mizukami Y, Nonomura A, Yamada T, Kurumaya H, Hayashi M, Koyasaki N, Taniya T, Noguchi M, Nakamura S, Matsubara F: Immunohistochemical demonstration of growth factors, TGFα, TGFβ, IGF-I andneu oncogene product in benign and malignant human breast tissues. Anticancer Res 10:1115–1126, 1990
Lundy J, Scuss A, Stanick D, McCormack ES, Kramer S, Sorvillo JM: Expression ofneu protein, EGF and TGFα in breast cancer. Am J Pathol 138:1527–1534, 1991
Umekita Y, Enokizono N, Sagara Y, Kuriwaki K, Takasaki T, Yoshida A, Yoshida H: Immunohistochemical studies on TGFα in human breast cancer: their relationship to estrogen receptor status, histological grade, mitogenic index and nodal status. Arch Pathol Hist 420:345–351, 1992
Qi C, Liscia DS, Normanno N, Merlo G, Johnson GR, Gullick WJ, Ciardiello F, Brandt R, Kim N, Kenney N, Salomon DS: Expression of transforming growth factor alpha, amphiregulin, and cripto-1 in human breast carcinomas. Br J Cancer, submitted, 1993
Arteaga CL, Hanauske AR, Clark GM, Osborne CK, Hazarika P, Pardue RL, Tio F, Von Hoff DD: Immunoreactive α transforming growth factor activity in effusions from cancer patients as a marker of tumor burden and patients prognosis. Cancer Res 48:5023–5028, 1988
Zwiebel JA, Bano M, Nexo E, Salomon DS, Kidwell WR: Partial purification of transforming growth factors from human milk. Cancer Res 46:933–939, 1986
Snedeker S, Brown C, Di Augustine R: Expression and functional properties of transforming growth factor α and epidermal growth factor during mouse mammary gland ductal morphogenesis. Proc Natl Acad Sci USA 88:276–280, 1991
Liscia DS, Merlo G, Ciardiello F, Kim N, Smith G, Callahan R, Salomon DS: Transforming growth factor-alpha messenger RNA localization in the developing adult rat and human mammary gland byin situ hybridization. Dev Biol 140:123–131, 1990
Salomon DS, Kidwell WR, Kim N, Ciardiello F, Bates SE, Valverius EM, Lippman ME, Dickson RB, Stampfer M: Modulation by estrogen and growth factors of transforming growth factor alpha (TGFα) expression in normal and malignant human mammary epithelial cells. Recent Results Cancer Res 113:57–69, 1989
Salomon DS, Ciardiello F, Valverius EM, Saeki T, Kim N: Transforming growth factors in human breast cancer. Biomed Pharmacother 43:661–667, 1989
Kenney N, Johnson GR, Selvam MP, Kim N, Qi C, Saeki T, Brandt R, Ciardiello F, Shoyab M, Plowman GD, Day A, Normanno N, Salomon DS: Transforming growth factor alpha (TGFα) and amphiregulin (AR) as autocrine growth factors in nontransformed, immortalized 184A1N4 human mammary epithelial cells. Mol Cell Diff 1:163–184, 1993
Shoyab M, McDonald V, Garrett Bradley J, Todaro GJ: Amphiregulin: a bifunctional growth-modulating glycoprotein produced by the phorbol 12-myristate 13-acetate-treated human breast adenocarcinoma cell line MCF-7. Proc Natl Acad Sci USA 85:6528–6532, 1988
Shoyab M, Plowman GD, McDonald VL, Bradley JG, Todaro GJ: Structure and function of human amphiregulin: a member of the epidermal growth factor family. Science 243:1074–1076, 1989
Plowman GD, Green JM, McDonald VL, Neubauer MG, Disteche CM, Todaro GJ, Shoyab M: The amphiregulin gene encodes a novel epidermal growth factor-related protein with tumor-inhibitory activity. Mol Cell Biol 10:1969–1981, 1990
Johnson GR, Kannan B, Shoyab M, Stromberg K: Amphiregulin induces tyrosine phosphorylation of the epidermal growth factor receptor and p185erbB-2. Evidence that amphiregulin acts exclusively through the epidermal growth factor receptor at the surface of human epithelial cells. J Biol Chem 268:2924–2931, 1993
Modrell B, McDonald V, Shoyab M: The interaction of amphiregulin with nuclei and putative nuclear localization sequence binding proteins. Growth Factors 7:195–205, 1992
Saeki T, Chen-Feng Q, Johnson GR, Gullick W, Tahara E, Normanno N, Ciardiello F, Kenney N, Stromberg K, Salomon DS: Differential immunohistochemical localization of amphiregulin and cripto in human normal colon and colorectal tumors. Cancer Res 52:3467–3473, 1991
Johnson GR, Saeki T, Auersperg NA, Gordon A, Shoyab M, Salomon DS, Stromberg K: Response to and expression of amphiregulin by ovarian carcinoma and normal ovarian surface epithelial cells: nuclear localization of endogenous amphiregulin. Biochem Biophys Res Commun 180:481–488, 1991
Li S, Plowman GD, Buckley SD, Shipley GD: Heparin inhibition of autonomous growth implicates amphiregulin as an autocrine growth factor for normal human mammary epithelial cells. J Cell Physiol 153:103–111, 1992
Cook PW, Mattox PA, Keeble WW, Pittelkow MR, Plowman GD, Shoyab M, Adelman JP, Shipley GD: A heparin sulfate-regulated human keratinocyte autocrine factor is similar or identical to amphiregulin. Mol Cell Biol 11:2547–2557, 1991
Cook PW, Pittelkow MR, Keeble WW, Graves-Deal R, Coffey RJ Jr, Shipley GD: Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. Cancer Res 52:3224–3227, 1992
Normanno N, Cheng-Feng Qi, Gullick WJ, Persico MG, Yarden Y, Wen D, Plowman GD, Kenney N, Johnson GR, Kim N, Brandt R, Martinez-Lacaci, Dickson RB, Salomon DS: Expression of amphiregulin, cripto-1, and heregulin α in human breast cancer cells. Int J Oncol 2:903–911, 1993
Hyder SM, Stancel GM, Nawaz Z, McDonnell P, Loose-Mitchell DS: Identification of an estrogen response element in the 3'-flanking region of the murine c-fos protooncogene. J Biol Chem 267:18047–18054, 1992
Normanno N, Selvam MP, Qi C, Saeki T, Johnson GR, Kim N, Ciardiello F, Shoyab M, Plowman GD, Todaro GJ, Salomon DS: Amphiregulin as an autocrine growth factor for c-Ha-ras and c-erbB-2 transformed human mammary epithelial cells. Proc Natl Acad Sci USA, in press, 1994
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 53:3597–3602, 1993
Ullrich A, Schlessinger J: Signal transduction by receptors with tyrosine kinase activity. Cell 61:203–212, 1990
Hanks SK: Eucaryotic protein kinases. Curr Opin Cell Biol 1:369–383, 1993
Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, Seeburg PH, Liebermann FA, Schlessinger J, Francke U, Levinson A, Ullrich A: Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with Neu oncogene. Science 230:1132–1139, 1985
Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J: Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature 309:418–425, 1984
Ciocca DR, Fujimura FK, Tandon AK, Clark GM, Mark C, Leechen GJ, Pounds GW, Vendely P, Owens MA, Pandian MR, McGuire WL: Correlation of HER-2/neu amplification with expression and with other prognostic factors in 1103 breast cancers. J Natl Cancer Inst 84:1279–1282, 1992
Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL: Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182, 1987
Peles E, Bacus SS, Koski RA, Lu HS, Wen D, Ogden SG, Levy RB, Yarden Y: Isolation of theneu/HER-2 stimulatory ligand: a 44 kD glycoprotein that induces differentiation of mammary tumor cells. Cell 69:205–216, 1992
Wen D, Peles E, Cupples R, Suggs SV, Bacus SS, Luo Y, Trail G, Hu S, Silbiger SM, Levy RB: Neu differentiation factor: a transmembrane glycoprotein containing an EGF domain and an immunoglobulin homology unit. Cell 69:559–572, 1992
Goldman R, Ben-Levy R, Peles E, Yarden Y: Heterodimerization of theerbB-1 anderbB-2 receptors in human breast carcinoma cells: a mechanism for receptor transregulation. Biochemistry 29:11024–11028, 1990
Bacus SS, Stancovski I, Huberman E, Chin D, Hurwitz E, Mill GB, Ullrich A, Sela M., Yarden Y: Tumorinhibitory monoclonal antibodies to the HER-2/neu receptor induce differentiation of human breast cancer cells. Cancer Res 52:2580–2589, 1992
Bacus SS, Kiguchi K, Chin D, King CR, Huberman E: Differentiation of cultured breast cancer cells (AU-565 and MCF-7) associated with loss of cell surface HER-2/neu antigen. Mol Carcin 3:350–362, 1990
Peles E, Ben-Levy R, Tzahar E, Liu N, Wen D, Yarden Y: Cell-type specific interaction of Neu differentiation factor (NDF/heregulin) with Neu/HER-2 suggests complex ligand-receptor relationships. EMBO J 12:961–971, 1993
Orr-Urtreger A, Trakhtenbrot L, Ben-Levy R, Wen D, Rechavi G, Lonai P, Yarden Y: Neural expression and chromosomal mapping of Neu differentiation factor to 8p12–p21. Proc Natl Acad Sci USA 90:1867–1871, 1993
Lupu R, Wellstein A, Sheridan J, Ennis BW, Zugmaier G, Katz D, Lippman ME, Dickson RB: Purification and characterization of a novel growth factor from human breast cancer cells. Biochemistry 31:7330–7340, 1992
Lupu R, Colomer R, Kannan B, Lippman ME: Characterization of a growth factor that bind exclusively to theerbB-2 receptor and induces cellular response. Proc Natl Acad Sci USA 89:2287–2291, 1992
Lupu R, Colomer R, Zugmaier G, Sarup J, Shepard M, Slamon D, Lippman ME: Direct interaction of a ligand for theerbB-2 oncogene product with the EGF receptor and p185erbB-2. Science 249:1552–1555, 1990
Ignotz RA, Kelly B, Davis RJ, Massagué J: Biologically active precursor for transforming growth factor type alpha, released by retrovirally transformed cells. Proc Natl Acad Sci USA 83:6307–6311, 1986
Tarakhovsky A, Zaichuk T, Prassolov V, Butenko ZA: A 25 kDa polypeptide is the ligand for p185neu and is secreted by activated macrophages. Oncogene 6:2187–2196, 1991
Dobashi K, Davis JG, Mikami Y, Freeman JK, Hamuro J: Characterization of a neu/c-erbB-2 protein specific activating factor. Proc Natl Acad Sci USA 88:8582–8586, 1991
Huang SS, Huang JS: Purification and characterization of theneu/erbB2 ligand-growth factor from bovine kidney. J Biol Chem 267:11508–11512, 1992
Falls DL, Rosen KM, Corfas G, Lane WS, Fischbach GD: ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the NEU ligand family. Cell 72:801–815, 1993
Marchioni MA, Goodearl ADJ, Chen MS, et al: Glial growth factors are alternatively splicederbB-2 ligands expressed in nervous system. Nature 362:312–318, 1993
Doolittle RF, Feng DF, Johnson MS: Computer-based characterization of epidermal growth factor precursor. Nature 307:558–560, 1984
Derynck R, Roberts AB, Winkler ME, Chen EY, Goeddel DV: Human transforming growth factoralpha: precursor structure and expression in E. coli. Cell 38:287–297, 1984
Brown JP, Twardzik DR, Marquardt H, Todaro GJ: Vaccinia virus encodes a polypeptide homologous to epidermal growth factor and transforming growth factor α. Nature 313:491–492, 1985
Dono R, Montuori N, Rocchi M, De Ponti-Zilli L, Ciccodicola A, Persico MG: Isolation and characterization of the CRIPTO autosomal gene and its X-linked related sequence. Am J Hum Genet 49:555–565, 1991
Andrews PW: Retinoic acid induces neuronal differentiation of a cloned human embryonal carcinoma cell linein vitro. Dev Biol 103:285–293, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Normanno, N., Ciardiello, F., Brandt, R. et al. Epidermal growth factor-related peptides in the pathogenesis of human breast cancer. Breast Cancer Res Tr 29, 11–27 (1994). https://doi.org/10.1007/BF00666178
Issue Date:
DOI: https://doi.org/10.1007/BF00666178