Overproduction of cyclin D1 is dependent on activated mTORC1 signal in nasopharyngeal carcinoma: implication for therapy

Cancer Lett. 2009 Jun 28;279(1):47-56. doi: 10.1016/j.canlet.2009.01.020. Epub 2009 Feb 8.

Abstract

Activated mTOR was implicated to play a role in the carcinogenesis of nasopharyngeal carcinoma (NPC). However, the mechanism of activated mTOR/Complex1(mTORC1) signaling pathway in NPC development has not been well established. In this study, we correlated the expression of mTORC1 signal molecules and Cyclin D1 in NPC. We also investigated the effect of blocking mTORC1 signal with rapamycin and mTOR siRNA on Cyclin D1 expression in CNE-2 cells, as well as cell apoptosis and viability. We found a positive association of mTORC1 signal molecules and Cyclin D1 in NPC. Also, we found blockage mTORC1 inhibited Cyclin D1 expression in CNE-2 cells and enhanced cell apoptosis. Our results suggested that mTORC1 signal pathway might be a potential target for NPC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Apoptosis
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Case-Control Studies
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Cell Survival
  • Cyclin D1 / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiprotein Complexes / metabolism
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Nasopharyngeal Neoplasms / therapy
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Signal Transduction* / drug effects
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases
  • Time Factors
  • Transfection
  • Up-Regulation

Substances

  • Adaptor Proteins, Signal Transducing
  • CCND1 protein, human
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Multiprotein Complexes
  • Phosphoproteins
  • RNA, Small Interfering
  • Cyclin D1
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus