Prostate Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Prostate Cancer, including details on symptoms, genetics, screening, treatment, information.

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

Fukuchi J, Hiipakka RA, Kokontis JM, Hsu S, Ko AL, Fitzgerald ML, Liao S

Ben May Institute for Cancer Research and Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA.

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.

Published 2 November 2004 in Cancer Res, 64(21): 7682-5.
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