The Molecular and Cellular Biology of HER2/neu Gene Amplification/Overexpression and the Clinical Development of Herceptin (Trastuzumab) Therapy for Breast Cancer

  • Mark D. Pegram
  • Gottfried Konecny
  • Dennis J. Slamon
Part of the Cancer Treatment and Research book series (CTAR, volume 103)


Proto oncogenes represent a family of genes which when activated have been shown to play a role in the pathogenesis of a number of malignancies in vertebrate species including humans.1,2 In physiologic states these same genes are known to play a role in the normal cell growth control and differentiation. The HER2/neu gene is a member of the Type I receptor tyrosine kinase (RTK) group which is one of the subfamilies in the proto oncogene family and encodes a 185kD surface membrane receptor protein. This gene has been localized to chromosome 17q21,1 and the encoded protein is expressed in a wide variety of tissues including the skin, oral mucera, breast, ovary, endometrium, lung, liver, pancreas, small and large bowel, kidney, bladder and the central nervous system as well as some connective tissues.4–5 The exact physiological role of the HER2/neu protein in these tissues is not completely understood, but like other proto oncogenes it is believed to play an important signaling role in cellular proliferation and differentiation processes. Current data suggests that it forms hetero-dimers with other members of the RTKI family (such as HER 1, HER3 and HER4 in response to various ligands known as heregulins.6–8 Activation of HER2/neu results in an increase its kinase activity which in turn initiates signal transduction resulting in either cellular proliferation and/or differentiation, depending on the ligand as well as the conditions.9–14 In human breast cancers, a non-inherited alteration occurs in this gene in 25–30% of cases.


Breast Cancer Clin Oncol HER2 Overexpression HER2 Protein HER2 Gene Amplification 
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Copyright information

© Springer Science+Business Media New York 2000

Authors and Affiliations

  • Mark D. Pegram
    • 1
  • Gottfried Konecny
    • 1
  • Dennis J. Slamon
    • 1
  1. 1.Division of Hematology OncologyUCLA School of MedicineUSA

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