Regulation of estrogenic effects by beclin 1 in breast cancer cells

Academic Article

Abstract

  • Beclin 1 is an essential mediator of autophagy and a regulator of cell growth and cell death. We examined the effect of Beclin 1 overexpression on the action of estradiol (E2) and two antiestrogens, raloxifene and 4-hydroxytamoxifen, in estrogen receptor α (ERα)-positive MCF-7 breast cancer cells. [3H]-thymidine incorporation studies showed that Beclin 1-overexpressing cells (MCF-7.beclin) had a lower proliferative response to E2 compared with cells transfected with vector control (MCF-7.control). There was only a 35% increase in [3H]-thymidine incorporation, after 24 hours of E2 treatment of MCF-7.beclin cells compared with untreated cells, whereas this increase was 2-fold for MCF-7.control cells. E2-induced changes in the expression of early-response genes were examined by real-time quantitiative PCR. There were significant differences in the pattern of expression of E2-induced genes c-myc, c-fos, Erg-1, and Nur77 between MCF-7.beclin and MCF-7.control cells two hours after treatment. Although E2-induced growth of MCF-7.control cells was completely inhibited by 500 nmol/L raloxifene or 500 nmol/L 4-hydroxytamoxifen, these concentrations of antiestrogens had no significant effect on the growth of MCF-7.beclin cells. Confocal microscopic and coimmunoprecipitation studies showed evidence for colocalization and association of Beclin 1 and ERα. In addition, E2 caused a decrease in Akt phosphorylation in MCF-7.beclin cells, compared with a 3-fold increase in MCF-7 cells, five minutes after treatment. These results indicate that Beclin 1 can down-regulate estrogenic signaling and growth response, and contribute to the development of antiestrogen resistance. This observation might be useful to define and overcome antiestrogen resistance of breast cancer. ©2008 American Association for Cancer Research.
  • Authors

    Published In

  • Cancer Research  Journal
  • Digital Object Identifier (doi)

    Pubmed Id

  • 20559818
  • Author List

  • John S; Nayvelt I; Hsu HC; Yang PA; Liu W; Das GM; Thomas T; Thomas TJ
  • Start Page

  • 7855
  • End Page

  • 7863
  • Volume

  • 68
  • Issue

  • 19