Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer.
Summary of "Role of squalene synthase in prostate cancer risk and the biological aggressiveness of human prostate cancer."
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.Prostate Cancer and Prostatic Diseases advance online publication, 1 May 2012; doi:10.1038/pcan.2012.14.
Affiliation
Department of Urology, Gunma University Graduate School of Medicine, Maebashi, Japan.
Journal Details
This article was published in the following journal.
Name: Prostate cancer and prostatic diseases
ISSN: 1476-5608
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22546838
- DOI: http://dx.doi.org/10.1038/pcan.2012.14
Medical and Biotech [MESH] Definitions
Fenretinide
A synthetic retinoid that is used orally as a chemopreventive against prostate cancer and in women at risk of developing contralateral breast cancer. It is also effective as an antineoplastic agent.
Prostate-specific Antigen
A glycoprotein that is a kallikrein-like serine proteinase and an esterase, produced by epithelial cells of both normal and malignant prostate tissue. It is an important marker for the diagnosis of prostate cancer.
Squalene Monooxygenase
The second enzyme in the committed pathway for CHOLESTEROL biosynthesis, this enzyme catalyzes the first oxygenation step in the biosynthesis of STEROLS and is thought to be a rate limiting enzyme in this pathway. Specifically, this enzyme catalyzes the conversion of SQUALENE to (S)-squalene-2,3-epoxide.
Ultrasound, High-intensity Focused, Transrectal
Tissue ablation of the PROSTATE performed by ultrasound from a transducer placed in the RECTUM. The procedure is used to treat prostate cancer (PROSTATIC NEOPLASMS) and benign prostatic hypertrophy (PROSTATIC HYPERPLASIA).
Prostatic Secretory Proteins
Proteins secreted by the prostate gland. The major secretory proteins from the human prostate gland include PROSTATE-SPECIFIC ANTIGEN, prostate-specific acid phosphatase, prostate-specific membrane antigen, and prostate-specific protein-94.
PubMed Articles
ABSTRACT The study of genes involved in androgen pathway can contribute to a better knowledge of prostate cancer. Our aim was to examine if polymorphisms in prostate-specific antigen (PSA) and androge...
Recent interest has focused on the role that inflammation may play in the development of prostate cancer and whether use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) affects risk....
The additional value of TGFβ1 and IL-7 to predict the course of prostate cancer progression.
BACKGROUND: Given the fact that prostate cancer incidence will increase in the coming years, new prognostic biomarkers are needed with regard to the biological aggressiveness of...
PURPOSE: The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. Mdm2, Mdm4 and Hausp are all critical regulators of the p53 protein. Despite the importanc...
Discovery of a new 2-aminobenzhydrol template for highly potent squalene synthase inhibitors.
To obtain small and efficient squalene synthase inhibitors, a flexible 2-aminobenzhydrol open form structure was designed and showed potent inhibitory activity comparable to 4,1-benzoxazepin compounds...
Clinical Trials
Study of Prostate Cancer in Black and White U.S. Veterans
Prostate cancer is diagnosed in approximately 334,500 men each year and accounts for nearly 41,800 deaths in the United States. Prostate cancer is the leading cancer affecting veterans a...
RATIONALE: Vitamin E supplements may stop or delay the development of prostate cancer in patients who are at risk of prostate cancer or who have prostate cancer. It is not yet known which...
Vaccine Therapy Plus Biological Therapy in Treating Patients With Prostate Cancer
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growin...
Vaccine Therapy Plus Biological Therapy in Treating Patients With Relapsed Prostate Cancer
RATIONALE: Vaccines may make the body build an immune response to kill tumor cells. Biological therapies use different ways to stimulate the immune system and stop cancer cells from growin...
Biological Therapy in Treating Patients With Prostate Cancer
RATIONALE: Interleukin-2 may stimulate a person's white blood cells including natural killer cells to kill prostate cancer cells. Interferon gamma may interfere with the growth of the canc...
