Androgenic suppression of ATP-binding cassette transporter A1 expression in LNCaP human prostate cancer cells

Cancer Res. 2004 Nov 1;64(21):7682-5. doi: 10.1158/0008-5472.CAN-04-2647.

Abstract

Alteration of lipid metabolism is commonly observed in sex hormone-dependent cancer cells, yet its mechanistic involvement in cancer cell proliferation and progression is unclear. We have found that the expression of the cholesterol transporter, ATP-binding cassette transporter A1 (ABCA1), was 15- to 20-fold higher in androgen-dependent than in androgen-independent LNCaP human prostate cancer cells, indicating a possible relationship between the expression levels of ABCA1 and prostate cancer progression. On the basis of real-time quantitative PCR and Western blot analysis, expression of ABCA1 in androgen-dependent cells was inhibited by androgen. The antiandrogen Casodex blocked the effect of androgen, implicating the androgen receptor in regulation of ABCA1 expression by androgens. Using an ABCA1 promoter-reporter gene assay, androgenic suppression was observed at the transcriptional level in androgen-dependent but not in androgen-independent prostate cancer cells. ABCA1 appears to have a role in modulating cell proliferation because knockdown of ABCA1 expression by RNA interference in androgen-dependent cells increased their rate of proliferation. Therefore, a suppressive effect of androgen on ABCA1 expression may be one of the mechanisms by which androgens regulate proliferation in prostate cancer cells. Attenuated ABCA1 expression in androgen-independent cells thus may contribute, in part, to prostate cancer progression.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics*
  • Androgens / pharmacology*
  • Base Sequence
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Male
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Prostatic Neoplasms / metabolism*
  • RNA, Messenger / analysis

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Androgens
  • RNA, Messenger