Chemosensitization of HER-2/neu-overexpressing human breast cancer cells to paclitaxel (Taxol) by adenovirus type 5 E1A

Oncogene. 1997 Aug 18;15(8):953-60. doi: 10.1038/sj.onc.1201250.


Breast cancer cells that overexpress HER-2/neu are more resistant to chemotherapeutic agents such as paclitaxel (Taxol) and docetaxel (Taxotere) than those that do not overexpress HER-2/neu. In previous work, we showed that the adenovirus type 5 E1A can repress HER-2/neu expression at the transcriptional level. Here we first demonstrated that paclitaxel sensitivity correlates with HER-2/neu expression level in a panel of mouse fibroblasts expressing different levels of HER-2/ neu, and that downregulation of HER-2/neu expression by E1A sensitizes the cells to paclitaxel. To further test whether E1A can sensitize HER-2/neu-overexpressing human breast cancer cells to paclitaxel through E1A-mediated HER-2/neu repression, an adenoviral vector was used to transfer the E1A gene into two human breast cancer cell lines, MDA-MB-453 and MDA-MB-361, that overexpress HER-2/neu. After E1A delivery, we observed that HER-2/neu expression level was reduced, and cells were treated with paclitaxel. Cell proliferation assays showed a synergistic growth inhibition effect of E1A and paclitaxel. The synergistic effect was also confirmed by soft agar colony-formation assay. Breast cancer cell lines that express low levels of HER-2/neu, MDA-MB-435 and MDA-MB-231 cells showed no synergistic growth inhibition effect when treated on the same protocols. Thus, we concluded that the adenovirus type 5 E1A gene can sensitize paclitaxel-resistant HER-2/neu-overexpressing breast cancer cells to the drug by repressing HER-2/neu expression. This in turn may have important implications for the development of a novel therapy that combines chemotherapy and gene therapy.

Publication types

  • 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

  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / pharmacology*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / therapy
  • Cell Line
  • Down-Regulation
  • Drug Resistance
  • Gene Expression
  • Genes, erbB-2*
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Mice
  • Paclitaxel / pharmacology*
  • Tumor Cells, Cultured / drug effects


  • Adenovirus E1A Proteins
  • Antineoplastic Agents, Phytogenic
  • Paclitaxel