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

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- t...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2004-11, Vol.64 (21), p.7682-7685
Main Authors: FUKUCHI, Junichi, HIIPAKKA, Richard A, KOKONTIS, John M, HSU, Stephen, KO, Andrew L, FITZGERALD, Michael L, SHUTSUNG LIAO
Format: Article
Language:English
Subjects:
Androgens - pharmacology
Antineoplastic agents
ATP Binding Cassette Transporter 1
ATP-Binding Cassette Transporters - genetics
Base Sequence
Biological and medical sciences
Cell Line, Tumor
Gene Expression Regulation, Neoplastic - drug effects
Humans
Male
Medical sciences
Molecular Sequence Data
Pharmacology. Drug treatments
Promoter Regions, Genetic
Prostatic Neoplasms - metabolism
RNA, Messenger - analysis
Tumors
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Summary: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.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.can-04-2647