Dysregulation of cellular signaling by HER2/neu in breast cancer

Semin Oncol. 2003 Oct;30(5 Suppl 16):38-48. doi: 10.1053/j.seminoncol.2003.08.006.

Abstract

Human epidermal growth factor receptor-2 (HER2/neu; erbB2) belongs to a family of four transmembrane receptor tyrosine kinases involved in signal transduction pathways that regulate cell growth and proliferation. Amplification or overexpression of HER2/neu occurs in about 30% of human breast and ovarian cancers and is associated with a poor clinical outcome, including short survival time and short time to relapse. Recent advances in our understanding of HER2/neu signaling pathways have greatly increased our knowledge of breast cancer tumorigenesis and have provided new targets for treating breast and ovarian tumors that overexpress HER2/neu. This review will focus on the signaling network mediated by HER2/neu in breast cancer and discuss our understanding of these pathways, which seem to be particularly important in mediating cell survival and growth under a wide variety of circumstances in breast cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Cycle
  • Cytoskeletal Proteins
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-2
  • Humans
  • NF-kappa B
  • Nuclear Proteins*
  • Protein-Serine-Threonine Kinases*
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-mdm2
  • Receptor, ErbB-2* / physiology
  • Signal Transduction* / drug effects
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Wnt Proteins
  • Zebrafish Proteins*
  • beta Catenin

Substances

  • Antineoplastic Agents
  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • NF-kappa B
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Tumor Suppressor Protein p53
  • Wnt Proteins
  • Zebrafish Proteins
  • beta Catenin
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt