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Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer
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Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer
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Journal Article
Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer
2012
Overview
Background:
We previously conducted a genome-wide linkage analysis of Japanese nuclear families affected with prostate cancer and showed that the susceptibility to prostate cancer was closely linked to D8S550 at 8p23. The role of
farnesyl diphosphate farnesyltransferase
(
FDFT1
), which is located under the peak marker D8S550 at 8p23, and squalene synthase, the enzyme encoded by
FDFT1
, in prostate cancer was studied.
Methods:
The association among common variants of
FDFT1
with prostate cancer risk, the promoter activities of
FDFT1
with different genotypes and the effects of inhibition of squalene synthase were studied, and the
FDFT1
transcript levels of human prostate samples were quantified.
Results:
The A allele of rs2645429 was significantly associated with prostate cancer risk in a Japanese familial prostate cancer population. Rs2645429 was located in the promoter region of
FDFT1
, and the AA genotype showed significantly increased promoter activity. The knockdown of
FDFT1
mRNA expression or squalene synthase inhibition led to a significant decrease in prostate cancer cell proliferation. Additionally, human prostate cancer specimens expressed significantly higher levels of
FDFT1
mRNA compared with noncancerous specimens. Finally, aggressive cancers showed higher transcript levels.
Conclusions:
FDFT1
and its encoded enzyme, squalene synthase, may play an important role in prostate cancer development and its aggressive phenotypes.
Publisher
Springer Science and Business Media LLC,Nature Publishing Group UK,Nature Publishing Group
Subject
/ Adult
/ Aged
/ Alleles
/ Biomedical and Life Sciences
/ Enzymes
/ Farnesyl-Diphosphate Farnesyltransferase
/ Farnesyl-Diphosphate Farnesyltransferase - genetics
/ Genomes
/ Genotype
/ Humans
/ Japan
/ Ligases
/ Male
/ Polymorphism, Single Nucleotide
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - pathology
/ Risk
/ Squalene
