Med19 promotes breast cancer cell proliferation by regulating CBFA2T3/HEB expression

Breast Cancer. 2017 May;24(3):433-441. doi: 10.1007/s12282-016-0722-3. Epub 2016 Aug 29.

Abstract

Background: Mediator complex 19 (Med19) is a pivotal subunit of the Mediator complex, and its aberrant expression is involved in tumourigenesis. We aimed to explore the mechanism by which Med19 promotes the proliferation of breast cancer.

Methods: Lentivirus-mediated inhibition of Med19, ectopic expression of Med19 and ectopic expression of core-binding factor subunit alpha 2 to translocation 3 (CBFA2T3) were applied in human breast cancer cell lines. Human breast cancer cell proliferation was determined using CCK8 and colony formation assays after lentivirus infection. The expression of Med19, CBFA2T3 and HEB was measured by real-time reverse transcription polymerase chain reaction and Western blotting. The correlation between Med19 and CBFA2T3 expression in tissue from 25 cases of human breast cancer was analysed.

Results: In this study, we demonstrate that cell proliferation and colony formation capacity were significantly inhibited after Med19 inhibition in vitro. The expression of CBFA2T3 was distinctly up-regulated in MDA-MB-231 and MCF-7 human breast cancer cells when Med19 was knocked down; however, the expression of HEB, which is targeted by CBFA2T3, was down-regulated. Meanwhile, ectopic expression of Med19 in BT-549 and Hs578T human breast cancer cells inhibited CBFA2T3 expression but enhanced HEB expression. The proliferation capacity of human breast cancer cells was increased when Med19 was overexpressed, but the effect of Med19 up-regulation could be reversed by CBFA2T3 overexpression. Furthermore, a negative correlation between Med19 and CBFA2T3 expression was demonstrated by Western blotting in human breast cancer tissue.

Conclusions: These results suggest that Med19 promotes breast cancer cell proliferation and that this effect is associated with CBFA2T3 and HEB. These results provide new insights into the potential role of Med19 in the regulation of breast carcinogenesis, and Med19 may be a useful therapeutic target in breast cancer therapy.

Keywords: Breast cancer; CBFA2T3; HEB; Med19; Proliferation.

MeSH terms

  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mediator Complex / genetics
  • Mediator Complex / metabolism*
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CBFA2T3 protein, human
  • MED19 protein, human
  • Mediator Complex
  • Repressor Proteins
  • Tumor Suppressor Proteins
  • TCF12 protein, human