Trichostatin A and Tamoxifen inhibit breast cancer cell growth by miR-204 and ERα reducing AKT/mTOR pathway

Biochem Biophys Res Commun. 2015 Nov 13;467(2):242-7. doi: 10.1016/j.bbrc.2015.09.182. Epub 2015 Oct 5.

Abstract

MicroRNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Increasing evidence suggests that miRNAs are functionally important in cancers. We demonstrated miR-204 exerts its function by targeting gene involved in tumor growth and chemotherapy drugs reactivity. Here, we show that Trichostatin A (TSA) could increase ERα expression in MCF-7 and MDA-MB-231 cells by reducing miR204. Analysis of tumors growth inhibition shows that TSA promotes ERα expression, which could be reversed by miR-204 mimic transfection. When miR-204 is down regulated, the inhibition of TAM on breast cancer cells is enhanced. Caspase 3 activity is also increased. TSA and TAM combination inhibits Mcl-1 expression by decreasing phosphorylation of AKT induced by ERα increase in vivo and in vitro.

Keywords: Breast cancer; Cell inhibition; Estrogen receptors (ER); miR-204.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Antineoplastic Agents, Hormonal / pharmacology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line
  • Cell Proliferation / drug effects
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hydroxamic Acids / pharmacology
  • MCF-7 Cells
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Protein Synthesis Inhibitors / pharmacology
  • Proto-Oncogene Proteins c-akt / genetics*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism
  • Tamoxifen / pharmacology
  • Tumor Burden / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Hormonal
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • Hydroxamic Acids
  • MIRN204 microRNA, human
  • MicroRNAs
  • Protein Synthesis Inhibitors
  • Tamoxifen
  • trichostatin A
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases