The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells

Oncogene. 1997 Jul 31;15(5):537-47. doi: 10.1038/sj.onc.1201222.


Recent studies indicate that oncogenes may be involved in determining the sensitivity of human cancers to chemotherapeutic agents. To define the effect of HER-2/neu oncogene overexpression on sensitivity to chemotherapeutic drugs, a full-length, human HER-2/neu cDNA was introduced into human breast and ovarian cancer cells. In vitro dose-response curves following exposure to 7 different classes of chemotherapeutic agents were compared for HER-2- and control-transfected cells. Chemosensitivity was also tested in vivo for HER-2- and control-transfected human breast and ovarian cancer xenografts in athymic mice. These studies indicate that HER-2/neu overexpression was not sufficient to induce intrinsic, pleomorphic drug resistance. Furthermore, changes in chemosensitivity profiles resulting from HER-2/neu transfection observed in vitro were cell line specific. In vivo, HER-2/neu-overexpressing breast and ovarian cancer xenografts were responsive to different classes of chemotherapeutic drugs compared to control-treated xenografts with no statistically significant differences between HER-2/neu-overexpressing and nonoverexpressing xenografts. We found no instance in which HER-2/neu-overexpressing xenografts were rendered more sensitive to chemotherapeutic drugs in vivo. HER-2/neu-overexpressing xenografts consistently exhibited more rapid regrowth than control xenografts following initial response to chemotherapy suggesting that a high rate of tumor cell proliferation rather than intrinsic drug resistance may be responsible for the adverse prognosis associated with HER-2/neu overexpression in human cancers.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Cell Transplantation
  • Dose-Response Relationship, Drug
  • Drug Resistance, Neoplasm / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / genetics
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Retroviridae / genetics
  • Transfection
  • Transplantation, Heterologous
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Recombinant Proteins
  • Receptor, ErbB-2