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

  • Rebecca S. Muraoka-Cook
  • Shu-Mang Feng
  • Karen E. Strunk
  • H. Shelton EarpIIIEmail author
Article

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.

Keywords

Mammary development Growth inhibition HER4 and breast cancer 

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

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Rebecca S. Muraoka-Cook
    • 1
    • 2
  • Shu-Mang Feng
    • 1
  • Karen E. Strunk
    • 1
  • H. Shelton EarpIII
    • 1
    • 3
    • 4
    Email author
  1. 1.UNC-Lineberger Comprehensive Cancer CenterUniversity of North Carolina Chapel HillChapel HillUSA
  2. 2.Department of GeneticsUniversity of North Carolina School of MedicineChapel HillUSA
  3. 3.Department of MedicineUniversity of North Carolina School of MedicineChapel HillUSA
  4. 4.Department of PharmacologyUniversity of North Carolina School of MedicineChapel HillUSA

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