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Tumor Biology

, 32:1097 | Cite as

Androgen receptor W741C and T877A mutations in AIDL cells, an androgen-independent subline of prostate cancer LNCaP cells

  • Takashi Otsuka
  • Kazuhiro Iguchi
  • Kazuhiro Fukami
  • Kenichiro Ishii
  • Shigeyuki Usui
  • Yoshiki Sugimura
  • Kazuyuki Hirano
Research Article

Abstract

The androgen-independent LNCaP (AIDL) cell line was generated by maintaining prostate cancer LNCaP cells in a hormone-deprived medium. Notably, synthetic androgen R1881-related gene response is attenuated in AIDL cells as compared to the parental LNCaP cells. The aim of this study was to clarify the mechanisms underlying androgen sensitivity in AIDL cells. We first examined the expression of androgen receptor (AR) and its co-regulators. However, no significant difference in mRNA expression was found between LNCaP and AIDL cells. Remarkably, AR protein levels were induced by R1881 and DHT in LNCaP cells, but not in AIDL cells. We next performed the cDNA sequencing to detect mutations in the AR gene. The T877A mutation was detected both in LNCaP and AIDL cells. Furthermore, AIDL cells harbored a missense substitution (TGG → TGT) in the AR gene, which caused a point mutation at codon 741 (W741C). Double T877A and W741C AR mutants have been previously reported to exhibit reduced androgen sensitivity. Hence, the low-androgen-sensitive responses of AIDL cells may be explained, at least in part, by AR gene mutations.

Keywords

LNCaP AIDL Androgen sensitivity Androgen receptor Mutation 

Notes

Acknowledgments

This study was supported by a Grant-in-Aid from the Uehara Memorial Foundation and a Grant-in-Aid for Young Scientists (No. 21791514) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2011

Authors and Affiliations

  • Takashi Otsuka
    • 1
    • 2
  • Kazuhiro Iguchi
    • 1
  • Kazuhiro Fukami
    • 1
  • Kenichiro Ishii
    • 3
    • 4
  • Shigeyuki Usui
    • 1
  • Yoshiki Sugimura
    • 3
  • Kazuyuki Hirano
    • 1
  1. 1.Laboratory of PharmaceuticsGifu Pharmaceutical UniversityGifuJapan
  2. 2.Ogaki Municipal HospitalOgakiJapan
  3. 3.Department of Nephro-Urologic Surgery and AndrologyMie University Graduate School of MedicineTsuJapan
  4. 4.Mie University Graduate School of Regional Innovation StudiesTsuJapan

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