Skip to main content

Advertisement

SpringerLink
Log in

ErbB4/HER4: Role in Mammary Gland Development, Differentiation and Growth Inhibition

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

The ErbB receptor tyrosine kinase family has often been associated with increased growth of breast epithelial cells, as well as malignant transformation and progression. In contrast, ErbB4/HER4 exhibits unique attributes from a two step proteolytic cleavage which releases an 80 kilodalton, nuclear localizing, tyrosine kinase to a signal transduction mechanism that slows growth and stimulates differentiation of breast cells. This review provides an overview of ErbB4/HER4 in growth and differentiation of the mammary epithelium, including its physiologic role in development, the contrasting growth inhibition/tumor suppression and growth acceleration of distinct ErbB4/HER4 isoforms and a description of the unique cell cycle regulated pattern of nuclear HER4 ubiquitination and destruction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

Abbreviations

EGF:

epidermal growth factor

EGFR:

epidermal growth factor receptor

kDa:

kilodalton

RTK:

receptor tyrosine kinase

HB-EGF:

heparin binding epidermal growth factor-like factor

TACE:

tumor necrosis factor-alpha converting enzyme

GFP-CTHER4 :

GFP tagged HER4 C-terminus w/o the tyrosine kinase domain

Nrg3:

Neuregulin3

TEBs:

terminal end buds

PRL:

prolatin

MECs:

mammary epithelial cells

JAK2:

Janus kinase 2

STAT5a:

signal transducer and transcriptional activator 5a

APC/C:

anaphase promoting complex/cyclosome

HANs:

hyperplastic alveolar nodules

References

  1. Cohen S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem USA. 1962;237:1555–62.

    CAS  Google Scholar 

  2. Downward J, Yarden Y, Mayes E, Scrace G, Totty N, Stockwell P, et al. Close similarity of epidermal growth factor receptor and v-erb-B oncogene protein sequences. Nature 1984;307:521–7.

    Article  PubMed  CAS  Google Scholar 

  3. Carpenter G, King L Jr, Cohen S. Rapid enhancement of protein phosphorylation in A-431 cell membrane preparations by epidermal growth factor. J Biol Chem. 1979;254:4884–91.

    PubMed  CAS  Google Scholar 

  4. Earp HS, Dawson TL, Li X, Yu H. Heterodimerization and functional interaction between EGF receptor family members: a new signaling paradigm with implications for breast cancer research. Breast Cancer Res Treat. 1995;35:115–32.

    Article  PubMed  CAS  Google Scholar 

  5. Yarden Y, Sliwkowski MX. Untangling the ErbB signaling network. Nat Rev Mol Cell Biol. 2001;2:127–37.

    Article  PubMed  CAS  Google Scholar 

  6. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. Embo J. 2000;19:3159–67.

    Article  PubMed  CAS  Google Scholar 

  7. Stern DF. ErbBs in mammary development. Exp Cell Res. 2003;284:89–98.

    Article  PubMed  CAS  Google Scholar 

  8. Stern DF. Tyrosine kinase signaling in breast cancer: ErbB family receptor tyrosine kinases. Breast Cancer Res. 2000;2:176–83.

    Article  PubMed  CAS  Google Scholar 

  9. Hynes NE. ErbB2 activation and signal transduction in normal and malignant mammary cells. J Mammary Gland Biol Neoplasia. 1996;1:199–206.

    Article  PubMed  CAS  Google Scholar 

  10. Schechter AL, Hung MC, Vaidyanathan L, Weinberg RA, Yang-Feng TL, Francke U, et al. The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor. Science 1985;229:976–8.

    Article  PubMed  CAS  Google Scholar 

  11. King CR, Kraus MH, Aaronson SA. Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 1985;229:974–6.

    Article  PubMed  CAS  Google Scholar 

  12. Plowman GD, Whitney GS, Neubauer MG, Green JM, McDonald VL, Todaro GJ, et al. Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci USA. 1990;87:4905–9.

    Article  PubMed  CAS  Google Scholar 

  13. Kraus MH, Issing W, Miki T, Popescu NC, Aaronson SA. Isolation and characterization of ERBB3, a third member of the ERBB/epidermal growth factor receptor family: evidence for overexpression in a subset of human mammary tumors. Proc Natl Acad Sci USA. 1989;86:9193–7.

    Article  PubMed  CAS  Google Scholar 

  14. Plowman GD, Culouscou JM, Whitney GS, Green JM, Carlton GW, Foy L, et al. Ligand-specific activation of HER4/p180erbB4, a fourth member of the epidermal growth factor receptor family. Proc Natl Acad Sci USA. 1993;90:1746–50.

    Article  PubMed  CAS  Google Scholar 

  15. Gschwind A, Fischer OM, Ullrich A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat Rev Cancer. 2004;4:361–70.

    Article  PubMed  CAS  Google Scholar 

  16. Troyer KL, Lee DC. Regulation of mouse mammary gland development and tumorigenesis by the ERBB signaling network. J Mammary Gland Biol Neoplasia. 2001;6:7–21.

    Article  PubMed  CAS  Google Scholar 

  17. Anderson NG, Ahmad T. ErbB receptor tyrosine kinase inhibitors as therapeutic agents. Front Biosci. 2002;7:1926–40.

    Article  Google Scholar 

  18. Hynes NE, Lane HA. ERBB receptors and cancer: the complexity of targeted inhibitors. Nat Rev Cancer. 2005;5:341–54.

    Article  PubMed  CAS  Google Scholar 

  19. Arteaga C. Targeting HER1/EGFR: a molecular approach to cancer therapy. Semin Oncol. 2003;30:3–14.

    CAS  Google Scholar 

  20. Lacenere CJ, Sternberg PW. Regulation of EGF receptor signaling in the fruitfly D. melanogaster and the nematode C. elegans. Breast Dis. 2000;11:19–30.

    PubMed  CAS  Google Scholar 

  21. Pinkas-Kramarski R, Alroy I, Yarden Y. ErbB receptors and EGF-like ligands: cell lineage determination and oncogenesis through combinatorial signaling. J Mammary Gland Biol Neoplasia. 1997;2:97–107.

    Article  PubMed  CAS  Google Scholar 

  22. Crovello CS, Lai C, Cantley LC, Carraway KL 3rd. Differential signaling by the epidermal growth factor-like growth factors neuregulin-1 and neuregulin-2. J Biol Chem. 1998;273:26954–61.

    Article  PubMed  CAS  Google Scholar 

  23. Daly JM, Olayioye MA, Wong AM, Neve R, Lane HA, Maurer FG, et al. NDF/heregulin-induced cell cycle changes and apoptosis in breast tumor cells: role of PI3 kinase and p38 MAP kinase pathways. Oncogene 1999;18:3440–51.

    Article  PubMed  CAS  Google Scholar 

  24. Falls DL. Neuregulins: functions, forms, and signaling strategies. Exp Cell Res. 2003;284:14–30.

    Article  PubMed  CAS  Google Scholar 

  25. Bianco C, Kannan S, De Santis M, Seno M, Tang CK, Martinez-Lacaci I, et al. Cripto-1 indirectly stimulates the tyrosine phosphorylation of erb B-4 through a novel receptor. J Biol Chem. 1999;274:8624–9.

    Article  PubMed  CAS  Google Scholar 

  26. Carpenter G. ErbB-4: mechanism of action and biology. Exp Cell Res. 2003;284:66–77.

    Article  PubMed  CAS  Google Scholar 

  27. Normanno N, Kim N, Wen D, Smith K, Harris AL, Plowman G, et al. Expression of messenger RNA for amphiregulin, heregulin, and cripto-1, three new members of the epidermal growth factor family, in human breast carcinomas. Breast Cancer Res Treat. 1995;35:293–7.

    Article  PubMed  CAS  Google Scholar 

  28. Riese DJ 2nd, Stern DF. Specificity within the EGF family/ErbB receptor family signaling network. Bioessays 1998;20:41–8.

    Article  PubMed  Google Scholar 

  29. Holmes WE, Sliwkowski MX, Akita RW, Henzel WJ, Lee J, Park JW, et al. Identification of heregulin, a specific activator of p185erbB2. Science 1992;256:1205–10.

    Article  PubMed  CAS  Google Scholar 

  30. Peles E, Bacus SS, Koski RA, Lu HS, Wen D, Ogden SG, Levy RB, et al. Isolation of the neu/HER-2 stimulatory ligand: a 44 kd glycoprotein that induces differentiation of mammary tumor cells. Cell 1992;69:205–16.

    Article  PubMed  CAS  Google Scholar 

  31. Vogt U, Bielawski K, Schlotter CM, Bosse U, Falkiewicz B, Podhajska AJ. Amplification of erbB-4 oncogene occurs less frequently than that of erbB-2 in primary human breast cancer. Gene 1998;223:375–80.

    Article  PubMed  CAS  Google Scholar 

  32. Abd El-Rehim DM, Ball G, Pinder SE, Rakha E, Paish C, Robertson JF, et al. High-throughput protein expression analysis using tissue microarray technology of a large well-characterized series identifies biologically distinct classes of breast cancer confirming recent cDNA expression analyses. Int J Cancer. 2005;116:340–50.

    Article  PubMed  CAS  Google Scholar 

  33. Suo Z, Risberg B, Kalsson MG, Willman K, Tierens A, Skovlund E, et al. EGFR family expression in breast carcinomas. c-erbB-2 and c-erbB-4 receptors have different effects on survival. J Pathol. 2002;196:17–25.

    Article  PubMed  CAS  Google Scholar 

  34. Witton CJ, Reeves JR, Going JJ, Cooke TG, Bartlett JM. Expression of the HER1–4 family of receptor tyrosine kinases in breast cancer. J Pathol. 2003;200:290–7.

    Article  PubMed  CAS  Google Scholar 

  35. Tovey SM, Witton CJ, Bartlett JM, Stanton PD, Reeves JR, Cooke TG. Outcome and human epidermal growth factor receptor (HER) 1–4 status in invasive breast carcinomas with proliferation indices evaluated by bromodeoxyuridine labeling. Breast Cancer Res. 2004;6:R246–51.

    Article  PubMed  CAS  Google Scholar 

  36. Bacus SS, Zelnick CR, Plowman G, Yarden Y. Expression of the erbB-2 family of growth factor receptors and their ligands in breast cancers. Implication for tumor biology and clinical behavior. Am J Clin Pathol. 1994;102:S13–24.

    PubMed  CAS  Google Scholar 

  37. Junttila TT, Sundvall M, Lundin M, Lundin J, Tanner M, Härkönen P, et al. Cleavable ErbB4 isoform in estrogen receptor-regulated growth of breast cancer cells. Cancer Res. 2005;65:1384–93.

    Article  PubMed  CAS  Google Scholar 

  38. Knowlden JM, Gee JM, Seery LT, Farrow L, Gullick WJ, Ellis IO, et al. c-erbB3 and c-erbB4 expression is a feature of the endocrine responsive phenotype in clinical breast cancer. Oncogene 1998;17:1949–57.

    Article  PubMed  CAS  Google Scholar 

  39. Pawlowski V, Révillion F, Hebbar M, Hornez L, Peyrat JP. Prognostic value of the type I growth factor receptors in a large series of human primary breast cancers quantified with a real-time reverse transcription-polymerase chain reaction assay. Clin Cancer Res. 2000;6:4217–25.

    PubMed  CAS  Google Scholar 

  40. Srinivasan R, Gillett CE, Barnes DM, Gullick WJ. Nuclear expression of the c-erbB-4/HER-4 growth factor receptor in invasive breast cancers. Cancer Res. 2000;60:1483–7.

    PubMed  CAS  Google Scholar 

  41. Barnes NL, Khavari S, Boland GP, Cramer A, Knox WF, Bundred NJ. Absence of HER4 expression predicts recurrence of ductal carcinoma in situ of the breast. Clin Cancer Res. 2005;11:2163–8.

    Article  PubMed  CAS  Google Scholar 

  42. Sartor CI, Zhou H, Kozlowska E, Guttridge K, Kawata E, Caskey L, et al. Her4 mediates ligand-dependent antiproliferative and differentiation responses in human breast cancer cells. Mol Cell Biol. 2001;21:4265–75.

    Article  PubMed  CAS  Google Scholar 

  43. Elenius K, Corfas G, Paul S, Choi CJ, Rio C, Plowman GD, et al. A novel juxtamembrane domain isoform of HER4/ErbB4. Isoform-specific tissue distribution and differential processing in response to phorbol ester. J Biol Chem. 1997;272:26761–8.

    Article  PubMed  CAS  Google Scholar 

  44. Gilbertson R, Hernan R, Pietsch T, Pinto L, Scotting P, Allibone R, et al. Novel ERBB4 juxtamembrane splice variants are frequently expressed in childhood medulloblastoma. Genes Chromosomes Cancer 2001;31:288–94.

    Article  PubMed  CAS  Google Scholar 

  45. Elenius K, Choi CJ, Paul S, Santiestevan E, Nishi E, Klagsbrun M. Characterization of a naturally occurring ErbB4 isoform that does not bind or activate phosphatidyl inositol 3-kinase. Oncogene 1999;18:2607–15.

    Article  PubMed  CAS  Google Scholar 

  46. Kainulainen V, Sundvall M, Maatta JA, Santiestevan E, Klagsbrun M, Elenius K. A natural ErbB4 isoform that does not activate phosphoinositide 3-kinase mediates proliferation but not survival or chemotaxis. J Biol Chem. 2000;275:8641–9.

    Article  PubMed  CAS  Google Scholar 

  47. Rio C, Buxbaum JD, Peschon JJ, Corfas G. Tumor necrosis factor-alpha-converting enzyme is required for cleavage of erbB4/HER4. J Biol Chem. 2000;275:10379–87.

    Article  PubMed  CAS  Google Scholar 

  48. Vecchi M, Rudolph-Owen LA, Brown CL, Dempsey PJ, Carpenter G. Tyrosine phosphorylation and proteolysis. Pervanadate-induced, metalloprotease-dependent cleavage of the ErbB-4 receptor and amphiregulin. J Biol Chem. 1998;273:20589–95.

    Article  PubMed  CAS  Google Scholar 

  49. Ni CY, Murphy MP, Golde TE, Carpenter G. g-Secretase cleavage and nuclear localization of ErbB-4 receptor tyrosine kinase. Science 2001;294:2179–81.

    Article  PubMed  CAS  Google Scholar 

  50. Lee HJ, Jung KM, Huang YZ, Bennett LB, Lee JS, Mei L, et al. Presenilin-dependent g-secretase-like intramembrane cleavage of ErbB4. J Biol Chem. 2002;277:6318–23.

    Article  PubMed  CAS  Google Scholar 

  51. Vidal GA, Naresh A, Marrero L, Jones FE. Presenilin-dependent g-secretase processing regulates multiple ERBB4/HER4 activities. J Biol Chem. 2005;280:19777–83.

    Article  PubMed  CAS  Google Scholar 

  52. Muraoka-Cook RS, Sandahl M, Husted C, Hunter D, Miraglia L, Feng SM, et al. The intracellular domain of ErbB4 induces differentiation of mammary epithelial cells. Mol Biol Cell. 2006;17:4118–29.

    Article  PubMed  CAS  Google Scholar 

  53. Long W, Wagner KU, Lloyd KC, Binart N, Shillingford JM, Hennighausen L, et al. Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5. Development 2003;130:5257–68.

    Article  PubMed  CAS  Google Scholar 

  54. Zhang M, Ding D, Salvi R. Expression of heregulin and ErbB/Her receptors in adult chinchilla cochlear and vestibular sensory epithelium. Hear Res. 2002;169:56–68.

    Article  PubMed  CAS  Google Scholar 

  55. Feng SM, Sartor CI, Hunter D, Zhou H, Yang X, Caskey LS, et al. The HER4 cytoplasmic domain, but not its C terminus, inhibits mammary cell proliferation. Mol Endocrinol. 2007;21:1861–76.

    Article  PubMed  CAS  Google Scholar 

  56. Strunk KE, Husted C, Miraglia LC, Sandahl M, Rearick WA, Hunter DM, et al. HER4 D-box sequences regulate mitotic progression and degradation of the nuclear HER4 cleavage product s80HER4. Cancer Res. 2007;67:6582–90.

    Article  PubMed  CAS  Google Scholar 

  57. Naresh A, Long W, Vidal GA, Wimley WC, Marrero L, Sartor CI, et al. The ERBB4/HER4 intracellular domain 4ICD is a BH3-only protein promoting apoptosis of breast cancer cells. Cancer Res. 2006;66:6412–2.

    Article  PubMed  CAS  Google Scholar 

  58. Chodosh LA. The reciprocal dance between cancer and development. N Engl J Med. 2002;347:134–6.

    Article  PubMed  Google Scholar 

  59. Howlin J, McBryan J, Martin F. Pubertal mammary gland development: insights from mouse models. J Mammary Gland Biol Neoplasia. 2006;11:283–97.

    Article  PubMed  Google Scholar 

  60. Howard B, Panchal H, McCarthy A, Ashworth A. Identification of the scaramanga gene implicates Neuregulin3 in mammary gland specification. Genes Dev. 2005;19:2078–90.

    Article  PubMed  CAS  Google Scholar 

  61. Schroeder JA, Lee DC. Dynamic expression and activation of ERBB receptors in the developing mouse mammary gland. Cell Growth Differ. 1998;9:451–64.

    PubMed  CAS  Google Scholar 

  62. Qu S, Rinehart C, Wu HH, Wang SE, Carter B, Xin H, et al. Gene targeting of ErbB3 using a Cre-mediated unidirectional DNA inversion strategy. Genesis 2006;44:477–86.

    Article  PubMed  CAS  Google Scholar 

  63. Horseman ND. Prolactin and mammary gland development. J Mammary Gland Biol Neoplasia. 1999;4:79–88.

    Article  PubMed  CAS  Google Scholar 

  64. Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA. Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev. 1998;19:225–68.

    Article  PubMed  CAS  Google Scholar 

  65. Brisken C, Kaur S, Chavarria TE, Binart N, Sutherland RL, Weinberg RA, et al. Prolactin controls mammary gland development via direct and indirect mechanisms. Dev Biol. 1999;210:96–106.

    Article  PubMed  CAS  Google Scholar 

  66. Grimm SL, Seagroves TN, Kabotyanski EB, Hovey RC, Vonderhaar BK, Lydon JP, et al. Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development. Mol Endocrinol. 2002;16:2675–91.

    Article  PubMed  CAS  Google Scholar 

  67. 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.

    Article  PubMed  CAS  Google Scholar 

  68. Long W, Wagner KU, Lloyd KC, Binart N, Shillingford JM, Hennighausen L, et al. Impaired differentiation and lactational failure of Erbb4-deficient mammary glands identify ERBB4 as an obligate mediator of STAT5. Development 2003;130:5257–68.

    Article  PubMed  CAS  Google Scholar 

  69. 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 USA. 2003;100:8281–6.

    Article  PubMed  CAS  Google Scholar 

  70. Wagner KU, Krempler A, Triplett AA, Qi Y, George NM, Zhu J, et al. Impaired alveologenesis and maintenance of secretory mammary epithelial cells in Jak2 conditional knockout mice. Mol Cell Biol. 2004;24:5510–20.

    Article  PubMed  CAS  Google Scholar 

  71. Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 1997;11:179–86.

    Article  PubMed  CAS  Google Scholar 

  72. Yu WH, Woessner Jr JF, McNeish JD, Stamenkovic I. CD44 anchors the assembly of matrilysin/MMP-7 with heparin-binding epidermal growth factor precursor and ErbB4 and regulates female reproductive organ remodeling. Genes Dev. 2002;16:307–23.

    Article  PubMed  CAS  Google Scholar 

  73. 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.

    Article  PubMed  CAS  Google Scholar 

  74. Williams CC, Allison JG, Vidal GA, Burow ME, Beckman BS, Marrero L, et al. The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. J Cell Biol. 2004;167:469–78.

    Article  PubMed  CAS  Google Scholar 

  75. Sardi SP, Murtie J, Koirala S, Patten BA, Corfas G. Presenilin-dependent ErbB4 nuclear signaling regulates the timing of astrogenesis in the developing brain. Cell 2006;127:185–97.

    Article  PubMed  CAS  Google Scholar 

  76. Muraoka-Cook RS, Caskey LS, Sandahl MA, Hunter DM, Husted C, Strunk KE, et al. Heregulin-dependent delay in mitotic progression requires HER4 and BRCA1. Mol Cell Biol. 2006;26:6412–24.

    Article  PubMed  CAS  Google Scholar 

  77. Tang CK, Concepcion XZ, Milan M, Gong X, Montgomery E, Lippman ME. Ribozyme-mediated down-regulation of ErbB-4 in estrogen receptor-positive breast cancer cells inhibits proliferation both in vitro and in vivo. Cancer Res. 1999;59:5315–22.

    PubMed  CAS  Google Scholar 

  78. Cohen BD, Green JM, Foy L, Fell HP. HER4-mediated biological and biochemical properties in NIH 3T3 cells. Evidence for HER1-HER4 heterodimers. J Biol Chem. 1996;271:4813–8.

    Article  PubMed  CAS  Google Scholar 

  79. Aqeilan RI, Donati V, Palamarchuk A, Trapasso F, Kaou M, Pekarsky Y, et al. WW domain-containing proteins, WWOX and YAP, compete for interaction with ErbB-4 and modulate its transcriptional function. Cancer Res. 2005;65:6764–72.

    Article  PubMed  CAS  Google Scholar 

  80. Omerovic J, Santangelo L, Puggioni EM, Marrocco J, Dall’Armi C, Palumbo C, et al. The E3 ligase Aip4/Itch ubiquitinates and targets ErbB-4 for degradation. Faseb J. 2007;21:2849–62.

    Article  PubMed  CAS  Google Scholar 

  81. Määttä JA, Sundvall M, Junttila TT, Peri L, Laine VJ, Isola J, et al. Proteolytic cleavage and phosphorylation of a tumor-associated ErbB4 isoform promote ligand-independent survival and cancer cell growth. Mol Biol Cell. 2006;17:67–79.

    Article  PubMed  Google Scholar 

  82. Aqeilan RI, Croce CM. WWOX in biological control and tumorigenesis. J Cell Physiol. 2007;212:307–10.

    Article  PubMed  CAS  Google Scholar 

  83. Komuro A, Nagai M, Navin NE, Sudol M. WW domain-containing protein YAP associates with ErbB-4 and acts as a co-transcriptional activator for the carboxyl-terminal fragment of ErbB-4 that translocates to the nucleus. J Biol Chem. 2003;278:33334–41.

    Article  PubMed  CAS  Google Scholar 

  84. Sundvall M, Peri L, Määttä JA, Tvorogov D, Paatero I, Savisalo M, et al. Differential nuclear localization and kinase activity of alternative ErbB4 intracellular domains. Oncogene 2007;26:6905–14.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UNC-Lineberger Comprehensive Cancer Center, University of North Carolina Chapel Hill, 450 West Ave CB 7295, Chapel Hill, NC, 27599, USA

    Rebecca S. Muraoka-Cook, Shu-Mang Feng, Karen E. Strunk & H. Shelton Earp III

  2. Department of Genetics, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA

    Rebecca S. Muraoka-Cook

  3. Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA

    H. Shelton Earp III

  4. Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, 27599, USA

    H. Shelton Earp III

Authors
  1. Rebecca S. Muraoka-Cook
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shu-Mang Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karen E. Strunk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Shelton Earp III
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Shelton Earp III.

Additional information

Financial and Material Support

NIH grant CA112553NIH SPORE CA58223

Breast Cancer Research Foundation

Rights and permissions

Reprints and permissions

About this article

Cite this article

Muraoka-Cook, R.S., Feng, SM., Strunk, K.E. et al. ErbB4/HER4: Role in Mammary Gland Development, Differentiation and Growth Inhibition. J Mammary Gland Biol Neoplasia 13, 235–246 (2008). https://doi.org/10.1007/s10911-008-9080-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-008-9080-x

Keywords

Search

Navigation