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Androgen Receptor-dependent Expression of Low-density Lipoprotein Receptor-related Protein 6 is Necessary for Prostate Cancer Cell Proliferation

  • Park, Eun (Department of Urology, Wallace Memorial Baptist Hospital) ;
  • Kim, Eun Kyoung (MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Minkyoung (MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine) ;
  • Ha, Jung Min (MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine) ;
  • Kim, Young Whan (MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine) ;
  • Jin, Seo Yeon (MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine) ;
  • Shin, Hwa Kyoung (Department of Anatomy, Pusan National University School of Korean Medicine) ;
  • Ha, Hong Koo (Department of Urology, Pusan National University Hospital) ;
  • Lee, Jeong Zoo (Department of Urology, Pusan National University Hospital) ;
  • Bae, Sun Sik (MRC for Ischemic Tissue Regeneration, Medical Research Institute, and Department of Pharmacology, Pusan National University School of Medicine)
  • Received : 2014.12.12
  • Accepted : 2015.04.08
  • Published : 2015.05.01

Abstract

Androgen receptor (AR) signaling is important for prostate cancer (PCa) cell proliferation. Here, we showed that proliferation of hormone-sensitive prostate cancer cells such as LNCaP was significantly enhanced by testosterone stimulation whereas hormone-insensitive prostate cancer cells such as PC3 and VCaP did not respond to testosterone stimulation. Blocking of AR using bicalutamide abolished testosterone-induced proliferation of LNCaP cells. In addition, knockdown of AR blocked testosterone-induced proliferation of LNCaP cells. Basal expression of low-density lipoprotein receptor-related protein 6 (LRP6) was elevated in VCaP cells whereas stimulation of testosterone did not affect the expression of LRP6. However, expression of LRP6 in LNCaP cells was increased by testosterone stimulation. In addition, knockdown of LRP6 abrogated testosterone-induced proliferation of LNCaP cells. Given these results, we suggest that androgen-dependent expression of LRP6 plays a crucial role in hormone-sensitive prostate cancer cell proliferation.

Keywords

References

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