A genetic screen in Drosophila for regulators of human prostate cancer progression

Biochem Biophys Res Commun. 2014 Sep 5;451(4):548-55. doi: 10.1016/j.bbrc.2014.08.015. Epub 2014 Aug 10.

Abstract

To uncover the mechanism by which human prostate cancer progresses, we performed a genetic screen for regulators of human prostate cancer progression using the Drosophila accessory gland, a functional homolog of the mammalian prostate. Cell growth and migration of secondary cells in the adult male accessory gland were found to be regulated by paired, N-cadherin, and E-cadherin, which are Drosophila homologues of regulators of human prostate cancer progression. Using this screening system, we also identified three genes that promoted growth and migration of secondary cells in the accessory gland. The human homologues of these candidate genes - MRGBP, CNPY2, and MEP1A - were found to be expressed in human prostate cancer model cells and to promote replication and invasiveness in these cells. These findings suggest that the development of the Drosophila accessory gland and human prostate cancer cell growth and invasion are partly regulated through a common mechanism. The screening system using the Drosophila accessory gland can be a useful tool for uncovering the mechanisms of human prostate cancer progression.

Keywords: Accessory gland; Drosophila; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / physiology
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Disease Progression*
  • Exocrine Glands / chemistry
  • Histone Acetyltransferases
  • Humans
  • Male
  • Metalloendopeptidases / genetics
  • Metalloendopeptidases / physiology
  • Neoplasm Invasiveness / physiopathology
  • Nuclear Proteins
  • Prostatic Neoplasms / physiopathology*

Substances

  • Adaptor Proteins, Signal Transducing
  • CNPY2 protein, human
  • Carrier Proteins
  • MRGBP protein, human
  • Nuclear Proteins
  • Histone Acetyltransferases
  • Metalloendopeptidases
  • meprin A