An activated mTOR/p70S6K signaling pathway in esophageal squamous cell carcinoma cell lines and inhibition of the pathway by rapamycin and siRNA against mTOR

Cancer Lett. 2007 Aug 18;253(2):236-48. doi: 10.1016/j.canlet.2007.01.026. Epub 2007 Mar 13.

Abstract

mTOR/p70S6K pathway is considered a central regulator in various malignant tumors, but its roles in esophageal squamous cell carcinoma (ESCC), which is a common cause of mortality in China, remain unknown. Here, we identify that the mTOR/p70S6K pathway is activated in ESCC; rapamycin and siRNA against mTOR rapidly inhibited expression of mTOR and the phosphorylation of its major downstream effectors, p70S6K and 4E-BP1, arrested cells in the G(0)/G(1) phase and induced apoptosis of ESCC cells. The findings may lay a foundation for making further investigations on the mTOR/p70S6K pathway as a potential target for ESCC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibiotics, Antineoplastic / pharmacology*
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / genetics
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Cell Proliferation
  • Esophageal Neoplasms / enzymology*
  • Esophageal Neoplasms / genetics
  • Humans
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / drug effects*
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • RNA, Small Interfering / pharmacology*
  • Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors*
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction / drug effects
  • Sirolimus / pharmacology*
  • TOR Serine-Threonine Kinases
  • Transfection
  • Up-Regulation / drug effects

Substances

  • Antibiotics, Antineoplastic
  • Protein Kinase Inhibitors
  • RNA, Small Interfering
  • Protein Kinases
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • Sirolimus