Pituitary tumor transforming gene binding factor (PBF) is required for androgen-induced prostate cancer proliferation and invasion

Neoplasma. 2019 May 23;66(3):327-335. doi: 10.4149/neo_2018_180730N552. Epub 2018 Dec 12.

Abstract

Pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene that plays a role in many cancers; however, its involvement in prostate cancer (PCa) remains unclear. Here, we examined PBF expression in clinical specimens and investigated its regulation and function in human PCa cell lines. Immunohistochemical staining of patient tissues revealed higher PBF expression in PCa than in benign prostatic hyperplasia or adjacent normal prostate specimens. In LNCaP and 22Rv1 cells, PBF expression was upregulated by androgen treatment in a manner partially blocked by the androgen receptor (AR) antagonist bicalutamide. We identified a novel androgen response element in the PBF gene promoter and demonstrated its functional relevance using luciferase reporter assays. Androgen treatment of LNCaP cells induced binding between the endogenous AR and the androgen response element in PBF, as measured by chromatin immunoprecipitation assays. Finally, RNA interference of PBF expression significantly reduced androgen-induced LNCaP cell growth and invasion. Thus, PBF is a novel AR target gene and plays a role in androgen-induced proliferation and metastatic functions in PCa cells.

MeSH terms

  • Androgens / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Neoplasm Invasiveness* / genetics
  • Neoplasm Invasiveness* / physiopathology
  • Prostatic Neoplasms* / genetics
  • Prostatic Neoplasms* / physiopathology
  • Protein Binding / drug effects
  • Proto-Oncogene Mas

Substances

  • Androgens
  • Intracellular Signaling Peptides and Proteins
  • MAS1 protein, human
  • Membrane Proteins
  • PTTG1IP protein, human
  • Proto-Oncogene Mas